Localization of Angiotensin II Type 1 receptor gene expression in rodent and human kidneys
Am J Physiol Renal Physiol. 2021 Feb 22. doi: 10.1152/ajprenal.00550.2020. Online ahead of print.ABSTRACTThe kidneys are an important target for angiotensin II (ANG II). In the adult kidneys the effects of ANG II are mediated mainly by ANG II type 1 (AT1) receptors. AT1 receptor expression has been reported for a variety of different cell types within the kidneys, suggesting a broad spectrum of actions for ANG II. Since there have been heterogeneous results in the literature regarding the intrarenal distribution of AT1 receptors, this study aimed to obtain a comprehensive overview about the localization of AT1 receptor exp...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Julia Schrankl Michaela Fuchs Katharina Broeker Christoph Daniel Armin Kurtz Charlotte Wagner Source Type: research

Calcineurin A-alpha suppression drives Nuclear Factor κB-mediated NADPH oxidase-2 upregulation
CONCLUSIONS: These findings indicate that 1) CnAα loss stimulates Nox2 upregulation, 2) NFκB is a novel CnAα-regulated transcription factor and 3) NFκB mediates CnAα-induced Nox2 and ROS upregulation.SIGNIFICANCE: Our results demonstrate that CnAα plays a key role in Nox2 and ROS generation. Further, these novel findings provide evidence of divergent CnA isoform signaling pathways. Finally, this study advocates for CnAα-sparing CNIs, ultimately circumventing the CNI nephrotoxicity.PMID:33615888 | DOI:10.1152/ajprenal.00254.2020 (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Aswathy M Cheriyan Adaku C Ume Cynthia E Francis Keyona N King Valerie A Linck Yun Bai Hui Cai Robert S Hoover Heping P Ma Jennifer L Gooch Clintoria R Williams Source Type: research

Overlapping roles of NADPH Oxidase 4 (Nox4) for diabetic and gadolinium-based contrast agent-induced systemic fibrosis
We examined the role of NADPH oxidase 4 (Nox4) in gadolinium-induced systemic disease. Age- and weight-matched mice were randomized to experimental diabetes (streptozotocin) and control followed by systemic gadolinium-based contrast agent treatment. Nox4-deficient mice were randomized to experimental diabetes and gadolinium-based contrast agent treatment. Skin fibrosis and cellular infiltration were apparent in both the gadolinium-based contrast agent-treated and experimental diabetes groups. Similarly, both groups demonstrated renal pathologies with evidence of reactive oxygen species generation. Deletion of Nox4 abrogate...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Francesca Bruno Joshua DeAguero Catherine Do Duck Yoon Lee Chunyan Tan G Patricia Escobar Brent Wagner Source Type: research

Regulated cell death in cisplatin-induced AKI: Relevance of myo-inositol metabolism
Am J Physiol Renal Physiol. 2021 Feb 22. doi: 10.1152/ajprenal.00016.2021. Online ahead of print.ABSTRACTRegulated cell death (RCD), distinct from accidental cell death, refers to a process ofwell-controlled programmed cell death with well-defined pathological mechanisms. In thepast few decades, various terms for RCDs were coined, and some of them have beenimplicated in the pathogenesis of various types of acute kidney injury (AKI). Cisplatin iswidely used as a chemotherapeutic drug for a broad spectrum of cancers, but its usagewas hampered because of being highly nephrotoxic. Cisplatin-induced AKI is commonlyseen clinical...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Fei Deng Xiaoping Zheng Isha Sharma Yingbo Dai Yinhuai Wang Yashpal S Kanwar Source Type: research

A novel STING antagonist H151 ameliorates cisplatin-induced acute kidney injury and mitochondrial dysfunction
Am J Physiol Renal Physiol. 2021 Feb 22. doi: 10.1152/ajprenal.00554.2020. Online ahead of print.ABSTRACTStimulator of interferon genes (STING) is an important adaptor in the cytosolic DNA sensing pathways. Recent study found that the deletion of STING ameliorated cisplatin-induced acute kidney injury (AKI), suggesting that STING could serve as a potential target for AKI therapy. Up to now, a series of small-molecule STING inhibitors/antagonists have been identified. However, none of research was performed to explore the role of human STING inhibitors in AKI. Here we investigated the effect of a newly generated covalent an...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Wei Gong Lingling Lu Yu Zhou Jiaye Liu Haoyang Ma Lvhan Fu Songming Huang Yue Zhang Aihua Zhang Zhanjun Jia Source Type: research

Role of the Polycystins as Mechanosensors of Extracellular Stiffness
Am J Physiol Renal Physiol. 2021 Feb 22. doi: 10.1152/ajprenal.00545.2020. Online ahead of print.ABSTRACTPolycystin-1 (PC-1) is a transmembrane protein, encoded by the PKD1 gene, mutated in Autosomal Dominant Polycystic Kidney Disease (ADPKD). This common genetic disorder, characterized by cyst formation in both kidneys, ultimately leading to renal failure, is still waiting for a definitive treatment. The overall function of PC-1 and the molecular mechanism responsible for cyst formation are slowly coming to light, but they are both still intensively studied. In particular, PC-1 has been proposed to act as a mechanosensor,...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Elisa A Nigro Alessandra Boletta Source Type: research

Soluble α-klotho anchors TRPV5 to the distal tubular cell membrane independent of FGFR1 by binding TRPV5 and galectin-1 simultaneously
Am J Physiol Renal Physiol. 2021 Feb 22. doi: 10.1152/ajprenal.00044.2021. Online ahead of print.ABSTRACTHypercalciuria is one of early manifestations of diabetic nephropathy (DN). This is partially due to a decrease in the expression of renal transient receptor potential vanilloid type 5 (TRPV5), which is responsible for renal calcium reabsorption. Soluble klotho was previously determined to increase TRPV5 by cleaving sialic acid, causing TRPV5 to bind to membrane protein galectin-1. However, a recent study showed that soluble klotho binds to α2-3-sialyllactose - where sialic acid is located - on TRPV5, rather than ...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Jinho Lee Kyung Don Ju Hyo Jin Kim Bodokhsuren Tsogbadrakh Hyunjin Ryu Eunjeong Jeong Kang Min Jeong Kang Jaeseok Yang Hee Kyung Kang Curie Ahn Kook-Hwan Oh Source Type: research

Localization of Angiotensin II Type 1 receptor gene expression in rodent and human kidneys
Am J Physiol Renal Physiol. 2021 Feb 22. doi: 10.1152/ajprenal.00550.2020. Online ahead of print.ABSTRACTThe kidneys are an important target for angiotensin II (ANG II). In the adult kidneys the effects of ANG II are mediated mainly by ANG II type 1 (AT1) receptors. AT1 receptor expression has been reported for a variety of different cell types within the kidneys, suggesting a broad spectrum of actions for ANG II. Since there have been heterogeneous results in the literature regarding the intrarenal distribution of AT1 receptors, this study aimed to obtain a comprehensive overview about the localization of AT1 receptor exp...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Julia Schrankl Michaela Fuchs Katharina Broeker Christoph Daniel Armin Kurtz Charlotte Wagner Source Type: research

Calcineurin A-alpha suppression drives Nuclear Factor κB-mediated NADPH oxidase-2 upregulation
CONCLUSIONS: These findings indicate that 1) CnAα loss stimulates Nox2 upregulation, 2) NFκB is a novel CnAα-regulated transcription factor and 3) NFκB mediates CnAα-induced Nox2 and ROS upregulation.SIGNIFICANCE: Our results demonstrate that CnAα plays a key role in Nox2 and ROS generation. Further, these novel findings provide evidence of divergent CnA isoform signaling pathways. Finally, this study advocates for CnAα-sparing CNIs, ultimately circumventing the CNI nephrotoxicity.PMID:33615888 | DOI:10.1152/ajprenal.00254.2020 (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Aswathy M Cheriyan Adaku C Ume Cynthia E Francis Keyona N King Valerie A Linck Yun Bai Hui Cai Robert S Hoover Heping P Ma Jennifer L Gooch Clintoria R Williams Source Type: research

Overlapping roles of NADPH Oxidase 4 (Nox4) for diabetic and gadolinium-based contrast agent-induced systemic fibrosis
We examined the role of NADPH oxidase 4 (Nox4) in gadolinium-induced systemic disease. Age- and weight-matched mice were randomized to experimental diabetes (streptozotocin) and control followed by systemic gadolinium-based contrast agent treatment. Nox4-deficient mice were randomized to experimental diabetes and gadolinium-based contrast agent treatment. Skin fibrosis and cellular infiltration were apparent in both the gadolinium-based contrast agent-treated and experimental diabetes groups. Similarly, both groups demonstrated renal pathologies with evidence of reactive oxygen species generation. Deletion of Nox4 abrogate...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Francesca Bruno Joshua DeAguero Catherine Do Duck Yoon Lee Chunyan Tan G Patricia Escobar Brent Wagner Source Type: research

Regulated cell death in cisplatin-induced AKI: Relevance of myo-inositol metabolism
Am J Physiol Renal Physiol. 2021 Feb 22. doi: 10.1152/ajprenal.00016.2021. Online ahead of print.ABSTRACTRegulated cell death (RCD), distinct from accidental cell death, refers to a process ofwell-controlled programmed cell death with well-defined pathological mechanisms. In thepast few decades, various terms for RCDs were coined, and some of them have beenimplicated in the pathogenesis of various types of acute kidney injury (AKI). Cisplatin iswidely used as a chemotherapeutic drug for a broad spectrum of cancers, but its usagewas hampered because of being highly nephrotoxic. Cisplatin-induced AKI is commonlyseen clinical...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Fei Deng Xiaoping Zheng Isha Sharma Yingbo Dai Yinhuai Wang Yashpal S Kanwar Source Type: research

A novel STING antagonist H151 ameliorates cisplatin-induced acute kidney injury and mitochondrial dysfunction
Am J Physiol Renal Physiol. 2021 Feb 22. doi: 10.1152/ajprenal.00554.2020. Online ahead of print.ABSTRACTStimulator of interferon genes (STING) is an important adaptor in the cytosolic DNA sensing pathways. Recent study found that the deletion of STING ameliorated cisplatin-induced acute kidney injury (AKI), suggesting that STING could serve as a potential target for AKI therapy. Up to now, a series of small-molecule STING inhibitors/antagonists have been identified. However, none of research was performed to explore the role of human STING inhibitors in AKI. Here we investigated the effect of a newly generated covalent an...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Wei Gong Lingling Lu Yu Zhou Jiaye Liu Haoyang Ma Lvhan Fu Songming Huang Yue Zhang Aihua Zhang Zhanjun Jia Source Type: research

Role of the Polycystins as Mechanosensors of Extracellular Stiffness
Am J Physiol Renal Physiol. 2021 Feb 22. doi: 10.1152/ajprenal.00545.2020. Online ahead of print.ABSTRACTPolycystin-1 (PC-1) is a transmembrane protein, encoded by the PKD1 gene, mutated in Autosomal Dominant Polycystic Kidney Disease (ADPKD). This common genetic disorder, characterized by cyst formation in both kidneys, ultimately leading to renal failure, is still waiting for a definitive treatment. The overall function of PC-1 and the molecular mechanism responsible for cyst formation are slowly coming to light, but they are both still intensively studied. In particular, PC-1 has been proposed to act as a mechanosensor,...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Elisa A Nigro Alessandra Boletta Source Type: research

Soluble α-klotho anchors TRPV5 to the distal tubular cell membrane independent of FGFR1 by binding TRPV5 and galectin-1 simultaneously
Am J Physiol Renal Physiol. 2021 Feb 22. doi: 10.1152/ajprenal.00044.2021. Online ahead of print.ABSTRACTHypercalciuria is one of early manifestations of diabetic nephropathy (DN). This is partially due to a decrease in the expression of renal transient receptor potential vanilloid type 5 (TRPV5), which is responsible for renal calcium reabsorption. Soluble klotho was previously determined to increase TRPV5 by cleaving sialic acid, causing TRPV5 to bind to membrane protein galectin-1. However, a recent study showed that soluble klotho binds to α2-3-sialyllactose - where sialic acid is located - on TRPV5, rather than ...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Jinho Lee Kyung Don Ju Hyo Jin Kim Bodokhsuren Tsogbadrakh Hyunjin Ryu Eunjeong Jeong Kang Min Jeong Kang Jaeseok Yang Hee Kyung Kang Curie Ahn Kook-Hwan Oh Source Type: research

Localization of Angiotensin II Type 1 receptor gene expression in rodent and human kidneys
Am J Physiol Renal Physiol. 2021 Feb 22. doi: 10.1152/ajprenal.00550.2020. Online ahead of print.ABSTRACTThe kidneys are an important target for angiotensin II (ANG II). In the adult kidneys the effects of ANG II are mediated mainly by ANG II type 1 (AT1) receptors. AT1 receptor expression has been reported for a variety of different cell types within the kidneys, suggesting a broad spectrum of actions for ANG II. Since there have been heterogeneous results in the literature regarding the intrarenal distribution of AT1 receptors, this study aimed to obtain a comprehensive overview about the localization of AT1 receptor exp...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Julia Schrankl Michaela Fuchs Katharina Broeker Christoph Daniel Armin Kurtz Charlotte Wagner Source Type: research

Calcineurin A-alpha suppression drives Nuclear Factor κB-mediated NADPH oxidase-2 upregulation
CONCLUSIONS: These findings indicate that 1) CnAα loss stimulates Nox2 upregulation, 2) NFκB is a novel CnAα-regulated transcription factor and 3) NFκB mediates CnAα-induced Nox2 and ROS upregulation.SIGNIFICANCE: Our results demonstrate that CnAα plays a key role in Nox2 and ROS generation. Further, these novel findings provide evidence of divergent CnA isoform signaling pathways. Finally, this study advocates for CnAα-sparing CNIs, ultimately circumventing the CNI nephrotoxicity.PMID:33615888 | DOI:10.1152/ajprenal.00254.2020 (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Aswathy M Cheriyan Adaku C Ume Cynthia E Francis Keyona N King Valerie A Linck Yun Bai Hui Cai Robert S Hoover Heping P Ma Jennifer L Gooch Clintoria R Williams Source Type: research

Overlapping roles of NADPH Oxidase 4 (Nox4) for diabetic and gadolinium-based contrast agent-induced systemic fibrosis
We examined the role of NADPH oxidase 4 (Nox4) in gadolinium-induced systemic disease. Age- and weight-matched mice were randomized to experimental diabetes (streptozotocin) and control followed by systemic gadolinium-based contrast agent treatment. Nox4-deficient mice were randomized to experimental diabetes and gadolinium-based contrast agent treatment. Skin fibrosis and cellular infiltration were apparent in both the gadolinium-based contrast agent-treated and experimental diabetes groups. Similarly, both groups demonstrated renal pathologies with evidence of reactive oxygen species generation. Deletion of Nox4 abrogate...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Francesca Bruno Joshua DeAguero Catherine Do Duck Yoon Lee Chunyan Tan G Patricia Escobar Brent Wagner Source Type: research

Regulated cell death in cisplatin-induced AKI: Relevance of myo-inositol metabolism
Am J Physiol Renal Physiol. 2021 Feb 22. doi: 10.1152/ajprenal.00016.2021. Online ahead of print.ABSTRACTRegulated cell death (RCD), distinct from accidental cell death, refers to a process ofwell-controlled programmed cell death with well-defined pathological mechanisms. In thepast few decades, various terms for RCDs were coined, and some of them have beenimplicated in the pathogenesis of various types of acute kidney injury (AKI). Cisplatin iswidely used as a chemotherapeutic drug for a broad spectrum of cancers, but its usagewas hampered because of being highly nephrotoxic. Cisplatin-induced AKI is commonlyseen clinical...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Fei Deng Xiaoping Zheng Isha Sharma Yingbo Dai Yinhuai Wang Yashpal S Kanwar Source Type: research

A novel STING antagonist H151 ameliorates cisplatin-induced acute kidney injury and mitochondrial dysfunction
Am J Physiol Renal Physiol. 2021 Feb 22. doi: 10.1152/ajprenal.00554.2020. Online ahead of print.ABSTRACTStimulator of interferon genes (STING) is an important adaptor in the cytosolic DNA sensing pathways. Recent study found that the deletion of STING ameliorated cisplatin-induced acute kidney injury (AKI), suggesting that STING could serve as a potential target for AKI therapy. Up to now, a series of small-molecule STING inhibitors/antagonists have been identified. However, none of research was performed to explore the role of human STING inhibitors in AKI. Here we investigated the effect of a newly generated covalent an...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Wei Gong Lingling Lu Yu Zhou Jiaye Liu Haoyang Ma Lvhan Fu Songming Huang Yue Zhang Aihua Zhang Zhanjun Jia Source Type: research

Role of the Polycystins as Mechanosensors of Extracellular Stiffness
Am J Physiol Renal Physiol. 2021 Feb 22. doi: 10.1152/ajprenal.00545.2020. Online ahead of print.ABSTRACTPolycystin-1 (PC-1) is a transmembrane protein, encoded by the PKD1 gene, mutated in Autosomal Dominant Polycystic Kidney Disease (ADPKD). This common genetic disorder, characterized by cyst formation in both kidneys, ultimately leading to renal failure, is still waiting for a definitive treatment. The overall function of PC-1 and the molecular mechanism responsible for cyst formation are slowly coming to light, but they are both still intensively studied. In particular, PC-1 has been proposed to act as a mechanosensor,...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Elisa A Nigro Alessandra Boletta Source Type: research

Soluble α-klotho anchors TRPV5 to the distal tubular cell membrane independent of FGFR1 by binding TRPV5 and galectin-1 simultaneously
Am J Physiol Renal Physiol. 2021 Feb 22. doi: 10.1152/ajprenal.00044.2021. Online ahead of print.ABSTRACTHypercalciuria is one of early manifestations of diabetic nephropathy (DN). This is partially due to a decrease in the expression of renal transient receptor potential vanilloid type 5 (TRPV5), which is responsible for renal calcium reabsorption. Soluble klotho was previously determined to increase TRPV5 by cleaving sialic acid, causing TRPV5 to bind to membrane protein galectin-1. However, a recent study showed that soluble klotho binds to α2-3-sialyllactose - where sialic acid is located - on TRPV5, rather than ...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Jinho Lee Kyung Don Ju Hyo Jin Kim Bodokhsuren Tsogbadrakh Hyunjin Ryu Eunjeong Jeong Kang Min Jeong Kang Jaeseok Yang Hee Kyung Kang Curie Ahn Kook-Hwan Oh Source Type: research

Localization of Angiotensin II Type 1 receptor gene expression in rodent and human kidneys.
Abstract The kidneys are an important target for angiotensin II (ANG II). In the adult kidneys the effects of ANG II are mediated mainly by ANG II type 1 (AT1) receptors. AT1 receptor expression has been reported for a variety of different cell types within the kidneys, suggesting a broad spectrum of actions for ANG II. Since there have been heterogeneous results in the literature regarding the intrarenal distribution of AT1 receptors, this study aimed to obtain a comprehensive overview about the localization of AT1 receptor expression in mouse, rat and human kidneys. Using the cell specific and high-resolution RN...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Schrankl J, Fuchs M, Broeker K, Daniel C, Kurtz A, Wagner C Tags: Am J Physiol Renal Physiol Source Type: research

Calcineurin A-alpha suppression drives Nuclear Factor κB-mediated NADPH oxidase-2 upregulation.
CONCLUSIONS: These findings indicate that 1) CnAα loss stimulates Nox2 upregulation, 2) NFκB is a novel CnAα-regulated transcription factor and 3) NFκB mediates CnAα-induced Nox2 and ROS upregulation. SIGNIFICANCE: Our results demonstrate that CnAα plays a key role in Nox2 and ROS generation. Further, these novel findings provide evidence of divergent CnA isoform signaling pathways. Finally, this study advocates for CnAα-sparing CNIs, ultimately circumventing the CNI nephrotoxicity. PMID: 33615888 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Cheriyan AM, Ume AC, Francis CE, King KN, Linck VA, Bai Y, Cai H, Hoover RS, Ma HP, Gooch JL, Williams CR Tags: Am J Physiol Renal Physiol Source Type: research

Overlapping roles of NADPH Oxidase 4 (Nox4) for diabetic and gadolinium-based contrast agent-induced systemic fibrosis.
We examined the role of NADPH oxidase 4 (Nox4) in gadolinium-induced systemic disease. Age- and weight-matched mice were randomized to experimental diabetes (streptozotocin) and control followed by systemic gadolinium-based contrast agent treatment. Nox4-deficient mice were randomized to experimental diabetes and gadolinium-based contrast agent treatment. Skin fibrosis and cellular infiltration were apparent in both the gadolinium-based contrast agent-treated and experimental diabetes groups. Similarly, both groups demonstrated renal pathologies with evidence of reactive oxygen species generation. Deletion of Nox4 abrogate...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Bruno F, DeAguero J, Do C, Lee DY, Tan C, Escobar GP, Wagner B Tags: Am J Physiol Renal Physiol Source Type: research

Regulated cell death in cisplatin-induced AKI: Relevance of myo-inositol metabolism.
Abstract Regulated cell death (RCD), distinct from accidental cell death, refers to a process ofwell-controlled programmed cell death with well-defined pathological mechanisms. In thepast few decades, various terms for RCDs were coined, and some of them have beenimplicated in the pathogenesis of various types of acute kidney injury (AKI). Cisplatin iswidely used as a chemotherapeutic drug for a broad spectrum of cancers, but its usagewas hampered because of being highly nephrotoxic. Cisplatin-induced AKI is commonlyseen clinically, and it also serves as a well-established prototypic model for laboratoryinvestigati...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Deng F, Zheng X, Sharma I, Dai Y, Wang Y, Kanwar YS Tags: Am J Physiol Renal Physiol Source Type: research

A novel STING antagonist H151 ameliorates cisplatin-induced acute kidney injury and mitochondrial dysfunction.
Abstract Stimulator of interferon genes (STING) is an important adaptor in the cytosolic DNA sensing pathways. Recent study found that the deletion of STING ameliorated cisplatin-induced acute kidney injury (AKI), suggesting that STING could serve as a potential target for AKI therapy. Up to now, a series of small-molecule STING inhibitors/antagonists have been identified. However, none of research was performed to explore the role of human STING inhibitors in AKI. Here we investigated the effect of a newly generated covalent antagonist H151 targeting both human and murine STING, in cisplatin-induced AKI. We found...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Gong W, Lu L, Zhou Y, Liu J, Ma H, Fu L, Huang S, Zhang Y, Zhang A, Jia Z Tags: Am J Physiol Renal Physiol Source Type: research

Role of the Polycystins as Mechanosensors of Extracellular Stiffness.
Abstract Polycystin-1 (PC-1) is a transmembrane protein, encoded by the PKD1 gene, mutated in Autosomal Dominant Polycystic Kidney Disease (ADPKD). This common genetic disorder, characterized by cyst formation in both kidneys, ultimately leading to renal failure, is still waiting for a definitive treatment. The overall function of PC-1 and the molecular mechanism responsible for cyst formation are slowly coming to light, but they are both still intensively studied. In particular, PC-1 has been proposed to act as a mechanosensor, although the precise signal that activates the mechanical properties of this protein h...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Nigro EA, Boletta A Tags: Am J Physiol Renal Physiol Source Type: research

Soluble α-klotho anchors TRPV5 to the distal tubular cell membrane independent of FGFR1 by binding TRPV5 and galectin-1 simultaneously.
Soluble α-klotho anchors TRPV5 to the distal tubular cell membrane independent of FGFR1 by binding TRPV5 and galectin-1 simultaneously. Am J Physiol Renal Physiol. 2021 Feb 22;: Authors: Lee J, Ju KD, Kim HJ, Tsogbadrakh B, Ryu H, Kang EJ, Kang MJ, Yang J, Kang HK, Ahn C, Oh KH Abstract Hypercalciuria is one of early manifestations of diabetic nephropathy (DN). This is partially due to a decrease in the expression of renal transient receptor potential vanilloid type 5 (TRPV5), which is responsible for renal calcium reabsorption. Soluble klotho was previously determined to increase TRPV5 by cleav...
Source: American Journal of Physiology. Renal Physiology - February 22, 2021 Category: Physiology Authors: Lee J, Ju KD, Kim HJ, Tsogbadrakh B, Ryu H, Kang EJ, Kang MJ, Yang J, Kang HK, Ahn C, Oh KH Tags: Am J Physiol Renal Physiol Source Type: research

Increased SGK1 activity potentiates mineralocorticoid/NaCl-induced kidney injury.
In conclusion, we propose that systemically increased SGK1 activity is a risk factor for the development of mineralocorticoid-dependent kidney injury in the context of low renal mass and independently of blood pressure. PMID: 33586495 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - February 15, 2021 Category: Physiology Authors: Sierra-Ramos C, Velazquez-Garcia S, Keskus AG, Vastola-Mascolo A, Rodríguez-Rodríguez AE, Luis-Lima S, Hernandez G, Navarro-Gonzalez JF, Porrini E, Konu O, Alvarez de la Rosa D Tags: Am J Physiol Renal Physiol Source Type: research

Dietary Salt Modifies the Blood Pressure Response to Renin-Angiotensin Inhibition in Experimental Chronic Kidney Disease.
rn EJ Abstract Chronic kidney disease (CKD) contributes to hypertension, but the mechanisms are incompletely understood. To address this, we applied the 5/6th nephrectomy rat model to characterize hypertension and the response to dietary salt and renin-angiotensin inhibition. 5/6th nephrectomy caused low-renin, salt-sensitive hypertension with hyperkalemia and unsuppressed aldosterone. Compared to sham, 5/6Nx rats had lower NHE3, NKCC2, NCC, a-ENaC and Kir4.1, but higher SKG1, prostasin, g-ENaC, and Kir5.1. These differences correlated with plasma renin, aldosterone, and/or potassium. On a normal salt diet, adrena...
Source: American Journal of Physiology. Renal Physiology - February 15, 2021 Category: Physiology Authors: Bovee DM, Uijl E, Severs D, Rubio-Beltrán E, van Veghel R, Maassen van den Brink A, Joles JA, Zietse R, Cuevas CA, Danser AHJ, Hoorn EJ Tags: Am J Physiol Renal Physiol Source Type: research

Lipotoxicity dysregulates immunoproteasome in podocytes and kidneys of type 2 diabetes.
Abstract Palmitic acid (PA) leads to lipotoxicity in type 2 diabetes and induces oxidative stress in podocytes. Oxidized cellular proteins are degraded by proteasomes. The role of proteasomes in PA- or oxidative stress- induced podocyte injury and pathogenesis of diabetic nephropathy (DN) is unknown. We investigated the effects of PA on expression of 20S and 26S proteasomes, proteasome activator 28 (PA28) regulators, and immunoproteasome in cultured podocytes and renal cortical tissues of db/dband db/m mice using Western blotting. Glomerular areas and glomerular basement membrane (GBM) widths of db/db and db/m mic...
Source: American Journal of Physiology. Renal Physiology - February 15, 2021 Category: Physiology Authors: Lee HS, Suh JY, Kang BC, Lee YJ Tags: Am J Physiol Renal Physiol Source Type: research

Salt Diet and the Dance of the Macula Densa Cells.
PMID: 33586498 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - February 15, 2021 Category: Physiology Authors: Cowley AW Tags: Am J Physiol Renal Physiol Source Type: research

Thick ascending limb claudins are altered to increase calciuria and magnesiuria in metabolic acidosis.
Abstract Urinary calcium and magnesium wasting is a characteristic feature of metabolic acidosis, and this study focused on the role of the thick ascending limb of Henle's loop in metabolic acidosis-induced hypercalciuria and hypermagnesiuria because thick ascending limb is an important site of paracellular calcium and magnesium reabsorption. Male Sprague-Dawley rats were used to determine the effects of acid loading (by adding NH4Cl 7.2 mmol/220 g BW/d to food slurry for 7 days) on renal expression of claudins and then to evaluate whether the results were reversed by antagonizing calcium-sensing receptor (using N...
Source: American Journal of Physiology. Renal Physiology - February 1, 2021 Category: Physiology Authors: Oh IH, Jo CH, Kim S, Jo S, Chung S, Kim GH Tags: Am J Physiol Renal Physiol Source Type: research

DPP4 inhibition mitigates Ang II-mediated kidney immune activation and injury in male mice.
Abstract Recent evidence suggests that DPP4 inhibition with saxagliptin (Saxa) is renoprotective in co-morbid conditions associated with activation of the renin-angiotensin-aldosterone system (RAAS), such as diabetes, obesity and hypertension, which confer a high cardiovascular risk. Immune system activation is now recognized as a contributor to RAAS-mediated tissue injury and, importantly, immunomodulatory effects of DPP4 have been reported. Accordingly, we examined the hypothesis that DPP4 inhibition with Saxa attenuates Ang II-induced kidney injury and albuminuria via attenuation of immune activation in the kid...
Source: American Journal of Physiology. Renal Physiology - February 1, 2021 Category: Physiology Authors: Nistala R, Meuth AI, Smith C, An J, Habibi J, Hayden M, Johnson MS, Aroor AR, Whaley-Connell A, Sowers JR, McKarns SR, Bender SB Tags: Am J Physiol Renal Physiol Source Type: research

Cleavage state of γENaC in mouse and rat kidney.
Cleavage state of γENaC in mouse and rat kidney. Am J Physiol Renal Physiol. 2021 Feb 01;: Authors: Frindt G, Shi S, Kleyman TR, Palmer LG Abstract Extracellular proteases can activate the epithelial Na channel (ENaC) by cleavage of the g subunit. Here we investigate the cleavage state of the channel in the kidneys of mice and rats on a low-salt diet. We identified the cleaved species of channels expressed in FRT cells by co-expressing the apical-membrane bound protease CAP1 (prostasin). To compare the peptides produced in the heterologous system with those in the mouse kidney we treated both ly...
Source: American Journal of Physiology. Renal Physiology - February 1, 2021 Category: Physiology Authors: Frindt G, Shi S, Kleyman TR, Palmer LG Tags: Am J Physiol Renal Physiol Source Type: research

A Plasma Creatinine- and Urea-Based Equation to Estimate Glomerular Filtration Rate in Rats.
In conclusion, applying this equation facilitates easy and repeatable estimates of GFR in rats. PMID: 33522412 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - February 1, 2021 Category: Physiology Authors: Besseling PJ, Pieters TT, Nguyen ITN, de Bree PM, Willekes N, Dijk AH, Bovée DM, Hoorn EJ, Rookmaaker MB, Gerritsen KG, Verhaar MC, Gremmels H, Joles JA Tags: Am J Physiol Renal Physiol Source Type: research

Epigenetic Regulation of Arginine Vasopressin Receptor 2 expression by PAX2 and Pax Transcription Interacting Protein.
In conclusion, PAX2 provides locus specificity for PTIP allowing the HMT complex to impart epigenetic changes at the Avpr2 locus and regulate Avpr2 transcription. These finding have major implications for understanding regulation of body water balance. PMID: 33522413 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - February 1, 2021 Category: Physiology Authors: Abraham S, Paknikar R, Bhumbra S, Luan D, Venkatareddy M, O'Connor CL, Bitzer M, Fenton RA, Hurd T, Garg P, Patel SR Tags: Am J Physiol Renal Physiol Source Type: research

Activation of hypoxia-sensing pathways promotes renal ischemic preconditioning following myocardial infarction.
Abstract Ischemic heart disease is the leading cause of death worldwide and is frequently comorbid with chronic kidney disease. Physiological communication is known to occur between the heart and the kidney and primary dysfunction in either organ can induce dysfunction in the other, a clinical entity known as cardiorenal syndrome, but mechanistic details are lacking. Here, we used a model of experimental myocardial infarction (MI) to test effects of chronic cardiac ischemia on acute and chronic kidney injury. Surprisingly, chronic cardiac damage protected animals from subsequent acute ischemic renal injury, an eff...
Source: American Journal of Physiology. Renal Physiology - February 1, 2021 Category: Physiology Authors: Terker AS, Sasaki K, Arroyo JP, Niu A, Wang S, Fan X, Zhang Y, Nwosisi S, Zhang MZ, Harris RC Tags: Am J Physiol Renal Physiol Source Type: research

Nicotine, Smoking, Podocytes and Diabetic Nephropathy.
Abstract Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease. Besides glycemic and blood pressure control, environmental factors such as cigarette smoking (CS) adversely affect the progression of DN. The effects of CS on DN progression have been attributed to combustion generated molecules without consideration to the role of nicotine (NIC), responsible for the addictive properties of both CS and electronic cigarettes (EC). Podocytes (POD) are essential to preserve the structure and function of the glomerular filtration barrier and strong evidence indicates that early POD loss promotes DN pr...
Source: American Journal of Physiology. Renal Physiology - January 18, 2021 Category: Physiology Authors: Jaimes EA, Zhou MS, Siddiqui M, Rezonzew G, Tian R, Seshan SV, Muwonge AN, Wong NJ, Azeloglu EU, Fornoni A, Merscher S, Raij L Tags: Am J Physiol Renal Physiol Source Type: research

The solute carrier SLC16A12 is critical for creatine and guanidinoacetate handling in the kidney.
Abstract A heterozygous mutation (c.643C.A; p.Q215X) in the creatine transporter SLC16A12 was proposed to cause a syndrome with juvenile cataracts, microcornea and glucosuria in humans. To further explore the role of SLC16A12 in renal physiology and decipher the mechanism underlying the phenotype of humans with the SLC16A12 mutation, we studied Slc16a12 knock-out (KO) rats. Slc16a12 KO rats had lower plasma levels and increased absolute and fractional urinary excretion of creatine and its precursor guanidinoacetate (GAA). Slc16a12 KO rats displayed lower plasma and urinary creatinine levels, but GFR was normal. Th...
Source: American Journal of Physiology. Renal Physiology - January 18, 2021 Category: Physiology Authors: Verouti SN, Lambert D, Mathis D, Pathare G, Escher G, Vogt B, Fuster DG Tags: Am J Physiol Renal Physiol Source Type: research

Acid-base events during hemodialysis.
PMID: 33439106 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - January 1, 2021 Category: Physiology Authors: Gennari FJ, Sargent JA Tags: Am J Physiol Renal Physiol Source Type: research

Reply to Gennari and Sargent: Acid-base events during hemodialysis.
PMID: 33439107 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - January 1, 2021 Category: Physiology Authors: Abramowitz MK Tags: Am J Physiol Renal Physiol Source Type: research

Urinary DPP4 correlates with renal dysfunction, and DPP4 inhibition protects against the reduction in megalin and podocin expression in experimental CKD.
This study investigated the molecular mechanisms underlying the antiproteinuric effect of DPP4 inhibition in 5/6 renal ablation rats and tested the hypothesis that the urinary activity of DPP4 correlates with chronic kidney disease (CKD) progression. Experiments were conducted in male Wistar rats who underwent 5/6 nephrectomy (Nx) or sham operation, followed by 8 weeks of treatment with the DPP4 inhibitor (DPP4i) sitagliptin or vehicle. Proteinuria increased progressively in Nx rats throughout the observation period. This increase was remarkably mitigated by sitagliptin. Higher levels of proteinuria in Nx rats compared to ...
Source: American Journal of Physiology. Renal Physiology - December 21, 2020 Category: Physiology Authors: Benetti A, Martins FL, Sene LB, Shimizu MHM, Seguro AC, Luchi WM, Girardi ACC Tags: Am J Physiol Renal Physiol Source Type: research

Role of γ-Adducin in Actin Cytoskeleton Rearrangements in Podocyte Pathophysiology.
Role of γ-Adducin in Actin Cytoskeleton Rearrangements in Podocyte Pathophysiology. Am J Physiol Renal Physiol. 2020 Dec 14;: Authors: Gao W, Liu Y, Fan L, Zheng B, Jefferson JR, Wang S, Zhang H, Fang X, Nguyen BV, Zhu T, Roman RJ, Fan F Abstract We recently reported that the enhanced susceptibility to chronic kidney disease (CKD) in the FHH rat is caused, at least in part, by a mutation in γ-adducin (ADD3) that attenuates renal vascular function. The present study explored whether Add3 contributes to the modulation of podocyte structure and function using FHH and FHH.Add3 transgenic rats....
Source: American Journal of Physiology. Renal Physiology - December 14, 2020 Category: Physiology Authors: Gao W, Liu Y, Fan L, Zheng B, Jefferson JR, Wang S, Zhang H, Fang X, Nguyen BV, Zhu T, Roman RJ, Fan F Tags: Am J Physiol Renal Physiol Source Type: research

Autoimmunity to urothelial antigen causes bladder inflammation, pelvic pain and voiding dysfunction: a novel animal model for Hunner type interstitial cystitis.
Abstract Recent evidence revealed that Hunner type interstitial cystitis (HIC) is a robust inflammatory disease potentially associated with enhanced immune responses and histologically characterized by epithelial denudation and lymphoplasmacytic infiltration with frequent clonal expansion of infiltrating B cells. To date, few animal models that reproduce the histological and clinical correlates of HIC have yet been established. In the present study, we aimed to develop a novel animal model for HIC via autoimmunity to the bladder urothelium using the transgenic mouse model (URO-OVA) that expresses the membrane form...
Source: American Journal of Physiology. Renal Physiology - December 14, 2020 Category: Physiology Authors: Akiyama Y, Yao JR, Kreder KJ, O'Donnell MA, Lutgendorf SK, Lyu D, Maeda D, Kume H, Homma Y, Luo Y Tags: Am J Physiol Renal Physiol Source Type: research

Development of a quantitative systems pharmacology model of chronic kidney disease - metabolic bone disorder.
Abstract Chronic kidney disease mineral bone disorder (CKD-MBD) is a virtually universal complication of kidney diseases, starting early in the course of disease and resulting in devastating clinical consequences ranging from bone fragility to accelerated atherosclerosis and early cardiovascular death. Guidelines for therapeutic goals for CKD-MBD have been published, and achievement of these guidelines is associated with improved survival. However, the incomplete understanding of CKD-MBD and the individual variability in the manifestations of CKD-MBD has made it difficult to achieve these guidelines. We hypothesiz...
Source: American Journal of Physiology. Renal Physiology - December 14, 2020 Category: Physiology Authors: Gaweda AE, McBride DE, Lederer ED, Brier ME Tags: Am J Physiol Renal Physiol Source Type: research

Sex Differences in Renal Ammonia Metabolism.
Abstract Sexual dimorphic variations are present in many aspects of biology and involve the structure and/or function of nearly every organ system. Acid-base homeostasis is critical for optimal health, and renal ammonia metabolism has a major role in the maintenance of acid-base homeostasis. Recent studies have shown sex-dependent differences in renal ammonia metabolism with regards to both basal ammonia excretion and the response to an exogenous acid load. These sexual dimorphisms are associated with structural changes in the proximal tubule and the collecting duct and variations in the expression of multiple pro...
Source: American Journal of Physiology. Renal Physiology - December 14, 2020 Category: Physiology Authors: Harris AN, Weiner ID Tags: Am J Physiol Renal Physiol Source Type: research

Exercise Intolerance in Kidney Diseases: Physiological Contributors and Therapeutic Strategies.
Abstract Exertional fatigue, defined as the overwhelming and debilitating sense of sustained exhaustion that impacts the ability to perform activities of daily living, is highly prevalent in chronic kidney disease (CKD) and end stage renal disease (ESRD). Subjective reports of exertional fatigue are paralleled by objective measurements of exercise intolerance throughout the spectrum of the disease. The prevalence of exercise intolerance is clinically noteworthy as it leads to increased frailty, worsened quality of life and an increased risk of mortality. The physiological underpinnings of exercise intolerance are ...
Source: American Journal of Physiology. Renal Physiology - December 7, 2020 Category: Physiology Authors: Kirkman DL, Bohmke N, Carbone S, Garten RS, Rodriguez-Miguelez P, Franco RL, Kidd JM, Abbate A Tags: Am J Physiol Renal Physiol Source Type: research

Mechanism of How Carbamylation Reduces Albumin Binding to FcRn contributing to increased vascular clearance.
Abstract Chronic kidney disease results in high serum urea concentrations leading to excessive protein carbamylation, primarily albumin. This is associated with increased cardiovascular disease and mortality. Multiple methods were used to address whether carbamylation alters albumin metabolism. Intravital 2-photon imaging of the Munich Wistar Fromter (MWF) rat kidney and liver allowed us to characterize filtration and proximal tubule and liver uptake. Microscale thermophoresis enabled quantification of Cubilin (CUB7,8 domain) and FcRn binding. Finally, multiple biophysical methods including dynamic light scatterin...
Source: American Journal of Physiology. Renal Physiology - December 7, 2020 Category: Physiology Authors: Yadav SPS, Sandoval R, Zhao J, Huang Y, Wang E, Kumar S, Campos-Bilderback SB, Rhodes GJ, Mechref Y, Molitoris BA, Wagner MC Tags: Am J Physiol Renal Physiol Source Type: research

Combination treatment with tenapanor and sevelamer synergistically reduces urinary phosphorus excretion in rats.
Abstract The majority of patients with chronic kidney disease (CKD) receiving dialysis do not reach target serum phosphorus concentrations, despite treatment with phosphate binders. Tenapanor is a non-binder, sodium/hydrogen exchanger isoform 3 (NHE3) inhibitor that reduces paracellular intestinal phosphate absorption. This pre-clinical study evaluated the effect of tenapanor and varying doses of sevelamer carbonate on urinary phosphorus excretion, a direct reflection of intestinal phosphate absorption. We measured 24-hour urinary phosphorus excretion in male rats assigned to groups dosed orally with vehicle or te...
Source: American Journal of Physiology. Renal Physiology - December 7, 2020 Category: Physiology Authors: King AJ, Kohler J, Fung C, Jiang Z, Quach A, Kumaraswamy P, Chertow GM, Rosenbaum DP Tags: Am J Physiol Renal Physiol Source Type: research