Activation of TGR5 restores AQP2 expression via HIF pathway in renal ischemia/reperfusion injury.
In conclusion, TGR5 stimulation by LCA prevented renal downregulation of AQPs in I/R injury, likely through activating HIF-1α signaling and suppressing inflammatory responses. PMID: 33427060 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - January 11, 2021 Category: Urology & Nephrology Authors: Han M, Li S, Xie H, Liu Q, Wang A, Hu S, Zhao X, Kong Y, Wang W, Li C Tags: Am J Physiol Renal Physiol Source Type: research

Proximal Tubule LPA1 and LPA2 Receptors use Divergent Signaling Pathways to Additively Increase Profibrotic Cytokine Secretion.
We report now that LPA1-receptor signaling through EGFR-ERK1/2-AP-1 co-operates with LPA2-dependent TGFB1 signaling to additively increase PDGFB/CTGF production and secretion by PT cells. Conversely, inhibition of both pathways results in greater suppression of PDGFB/CTGF production and secretion, and promotes greater PT cellular differentiation than inhibiting one pathway alone. Antagonism of LPA-generating enzyme autotaxin suppressed signaling through both pathways. After IRI, kidneys showed not only more LPA2, nuclear SMAD2/3 and PDGFB/CTGF, but also increased LPA1 and autotaxin proteins, together with enhanced EGFR/ERK...
Source: Am J Physiol Renal P... - January 11, 2021 Category: Urology & Nephrology Authors: Geng H, Lan R, Liu Y, Chen W, Wu M, Saikumar P, Weinberg JM, Venkatachalam MA Tags: Am J Physiol Renal Physiol Source Type: research

Activation of RAS contributes to peritoneal fibrosis via dysregulation of low-density lipoprotein receptor.
In conclusion, increased intracellular RAS activity impaired lipid homeostasis and induced ECM accumulation in HPMCs by disrupting the LDLr pathway, which contributed to PF. PMID: 33427062 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - January 11, 2021 Category: Urology & Nephrology Authors: Liu J, Feng Y, Li N, Shao QY, Zhang Q, Sun C, Xu P, Jiang CM Tags: Am J Physiol Renal Physiol Source Type: research

Role of SOLUBLE GUANYLYL CYCLASE in RENAL AFFERENT AND EFFERENT ARTERIOLES.
Abstract Renal arteriolar tone depends considerably on the dilatory action of nitric oxide (NO) via activation of soluble guanylyl cyclase (sGC) and cGMP action. NO deficiency and hypoxia/reoxygenation are important pathophysiological factors in the development of acute kidney injury. It is hypothesized that the NO-sGC-cGMP system functions differently in renal afferent (AA) compared to efferent arterioles (EA) and that the sGC activator cinaciguat differentially dilates these arterioles.Experiments were performed in isolated, perfused mouse glomerular arterioles. Hypoxia (0.1 % oxygen) was achieved by using a hyp...
Source: Am J Physiol Renal P... - December 28, 2020 Category: Urology & Nephrology Authors: Wennysia IC, Zhao L, Schomber T, Braun D, Golz S, Summer H, Benardeau A, Lai EY, Lichtenberger FB, Schubert R, Persson PB, Xu MZ, Patzak A Tags: Am J Physiol Renal Physiol Source Type: research

High salt intake induces collecting duct HDAC1-dependent NO signaling.
We reported that high salt intake stimulates renal collecting duct (CD) endothelin B receptor (ETBR)/NOS1β-dependent NO production inhibiting the epithelial sodium channel (ENaC) promoting natriuresis. However, the mechanism underlying the high salt (HS) induced increase of NO production is unclear. Histone deacetylase 1 (HDAC1) responds to increased fluid flow, as can occur in the CD during HS intake. The renal inner medulla (IM), in particular the IMCD, has the highest NOS1 activity within the kidney. Hence, we hypothesized that HS intake provokes HDAC1 activation of NO production in the IM. HS intake for one week s...
Source: Am J Physiol Renal P... - December 28, 2020 Category: Urology & Nephrology Authors: Sedaka RS, Hyndman KA, Mironova E, Stockand JD, Pollock JS Tags: Am J Physiol Renal Physiol Source Type: research

Effect of Forkhead Box O1 in Renal Tubular Epithelial Cells on Endotoxin-Induced Acute Kidney Injury.
In conclusion, downregulation of FOXO1 in RTECs mediated endotoxin-induced AKI and mitochondrial damage. Overexpression of FOXO1 could improve renal injury and mitochondrial dysfunction, and this effect occurred at least in part as a result of PGC1-α signaling. FOXO1 might be a potential target for the prevention and treatment of endotoxin-induced AKI. PMID: 33356954 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - December 28, 2020 Category: Urology & Nephrology Authors: Zhang M, Dong W, Li Z, Xiao Z, Xie Z, Ye Z, Liu S, Li R, Chen Y, Zhang L, Wang M, Liang H, Baihetiyaer R, Apaer R, Dong Z, Liang X Tags: Am J Physiol Renal Physiol Source Type: research

Environmental circadian disruption suppresses rhythms in kidney function and accelerates excretion of renal injury markers in urine of male hypertensive rats.
Abstract Non-traditional work schedules, such as shift work, have been associated with numerous health issues including cardiovascular and metabolic disease. These work schedules can chronically misalign environmental timing cues with internal circadian clock systems in the brain and in peripheral organs, leading to dysfunction of those systems and their associated biological processes. Environmental circadian disruption in the kidney may be an important factor in the increased incidence of hypertension and adverse health outcomes in human shift workers. The relationship between renal rhythmicity and injury resili...
Source: Am J Physiol Renal P... - December 28, 2020 Category: Urology & Nephrology Authors: Hill AM, Crislip GR, Stowie A, Ellis I, Ramsey A, Castanon-Cervantes O, Gumz ML, Davidson AJ Tags: Am J Physiol Renal Physiol Source Type: research

The Potential Role of the Na/K-ATPase and its Signaling in Development of Anemia in Chronic Kidney Disease.
Abstract Chronic kidney disease (CKD) is one of the most prominent diseases affecting our population today. According to the Factsheet published by Centers for Disease Control and Prevention (CDC), it effects approximately 15% of the total population in the United States in some way, shape, or form. Within the myriad of symptomatology associated with CKD, one of the most prevalent factors in terms of affecting quality of life is anemia. Anemia of CKD cannot be completely attributed to one mechanism or cause, but rather has a multifactorial origin in the pathophysiology of CKD. While briefly summarizing well-docume...
Source: Am J Physiol Renal P... - December 28, 2020 Category: Urology & Nephrology Authors: Maxwell KD, Chuang J, Chaudhry MA, Nie Y, Bai F, Sodhi K, Liu J, Shapiro JI Tags: Am J Physiol Renal Physiol Source Type: research

The oxygen cascade in hemodialysis patients and native high altitude dwellers- Lessons from extreme physiology to benefit patients with end-stage renal disease.
Abstract Hemodialysis patients repeatedly undergo intradialytic low arterial oxygen saturation, as well as low central venous oxygen saturation, reflecting an imbalance between upper body systemic oxygen supply and demand, which are associated with increased mortality. Abnormalities along the entire oxygen cascade, with impaired diffusive and convective oxygen transport, contribute to the reduced tissue oxygen supply. Dialysis treatment impairs pulmonary gas exchange and reduces ventilatory drive, whereas ultrafiltration can reduce tissue perfusion due to a decline in cardiac output. In addition to these factors, ...
Source: Am J Physiol Renal P... - December 28, 2020 Category: Urology & Nephrology Authors: Kooman JP, Stenvinkel P, Shiels PG, Feelisch M, Canaud B, Kotanko P Tags: Am J Physiol Renal Physiol Source Type: research

Vanderbilt O'Brien Kidney Center.
Abstract The Vanderbilt O'Brien Kidney Center (VOKC) is one of the eight NDDK-P30 funded Centers in the United States. The mission of these core-based Centers is to provide technical and conceptual support to enhance and facilitate research in the field of kidney diseases. The goal of the VOKC is to provide support to understand mechanisms and identify potential therapies for acute and chronic kidney disease. The services provided by the VOKC are meant to help the scientific community to have the right support and tools as well as to select the right animal model, statistical analysis, and clinical study design to...
Source: Am J Physiol Renal P... - December 28, 2020 Category: Urology & Nephrology Authors: Pozzi A, Harris RC Tags: Am J Physiol Renal Physiol Source Type: research

Am J Physiol Renal Physiol; +24 new citations
24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: Am J Physiol Renal Physiol These pubmed results were generated on 2020/12/16PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - December 16, 2020 Category: Urology & Nephrology Tags: Report Source Type: research

Corrigendum.
CORRIGENDUM. Am J Physiol Renal Physiol. 2020 Dec 01;319(6):F1000 Authors: PMID: 33210946 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - November 20, 2020 Category: Urology & Nephrology Tags: Am J Physiol Renal Physiol Source Type: research

O'Brien Kidney Research Centers.
PMID: 33166180 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - November 9, 2020 Category: Urology & Nephrology Authors: Staruschenko A, Brooks HL Tags: Am J Physiol Renal Physiol Source Type: research

Chronic intermittent hypoxia impairs diuretic and natriuretic responses to volume expansion in rats with preserved low-pressure baroreflex control of the kidney.
We examined the effects of exposure to chronic intermittent hypoxia (CIH) on baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory responses to volume expansion (VE) before and after intra-renal TRPV1 blockade by capsaizepine (CPZ). Male Wistar rats were exposed to 96 cycles of hypoxia per day for 14 days (CIH), or normoxia. Urine flow and absolute Na+ excretion during VE were less in CIH-exposed rats, but the progressive decrease in RSNA during VE was preserved. Assessment of the high-pressure baroreflex revealed an increase in the operating and response range of RSNA and decreased slope in CIH...
Source: Am J Physiol Renal P... - November 9, 2020 Category: Urology & Nephrology Authors: AlMarabeh S, O'Neill J, Cavers J, Lucking EF, O'Halloran KD, Abdulla MH Tags: Am J Physiol Renal Physiol Source Type: research

Overexpression of TGF- β1 induces renal fibrosis and accelerates the decline in kidney function in polycystic kidney disease.
Overexpression of TGF-β1 induces renal fibrosis and accelerates the decline in kidney function in polycystic kidney disease. Am J Physiol Renal Physiol. 2020 Nov 09;: Authors: Zhang Y, Dai Y, Raman A, Daniel E, Metcalf J, Reif GA, Pierucci-Alves F, Wallace DP Abstract Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the presence of numerous fluid-filled cysts, extensive fibrosis, and the progressive decline in kidney function. Transforming growth factor β1 (TGF-β1), an important mediator for renal fibrosis and chronic kidney disease, is overexpressed by cystic ce...
Source: Am J Physiol Renal P... - November 9, 2020 Category: Urology & Nephrology Authors: Zhang Y, Dai Y, Raman A, Daniel E, Metcalf J, Reif GA, Pierucci-Alves F, Wallace DP Tags: Am J Physiol Renal Physiol Source Type: research

Alkali supplementation as a therapeutic in chronic kidney disease: what mediates protection?
ALKALI SUPPLEMENTATION AS A THERAPEUTIC IN CHRONIC KIDNEY DISEASE: WHAT MEDIATES PROTECTION? Am J Physiol Renal Physiol. 2020 Nov 09;: Authors: Mannon EC, O'Connor PM Abstract Sodium bicarbonate (NaHCO3) has been recognized as a possible therapy to target chronic kidney disease (CKD) progression. Several small clinical trials have demonstrated that supplementation with NaHCO3 or other alkalizing agents slow renal functional decline in patients with CKD. While the benefits of NaHCO3 treatment have been thought to result from improving pH status, a number of studies now indicate that NaHCO3 or other alk...
Source: Am J Physiol Renal P... - November 9, 2020 Category: Urology & Nephrology Authors: Mannon EC, O'Connor PM Tags: Am J Physiol Renal Physiol Source Type: research

AJP-Renal Collections: Hypertension.
PMID: 33166184 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - November 9, 2020 Category: Urology & Nephrology Authors: Klemens CA, Staruschenko A Tags: Am J Physiol Renal Physiol Source Type: research

Silencing of the lncRNA TUG1 attenuates epithelial-mesenchymal transition of renal tubular epithelial cells by sponging miR-141-3p via regulating β-catenin.
In conclusion, TUG1 promotes EMT in TGF-β1-induced HK-2 cells by upregulating β-catenin levels through sponging miR-141-3p, suggesting a novel therapeutic candidate for RIF. PMID: 33135476 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - November 2, 2020 Category: Urology & Nephrology Authors: Zhang B, Zhao C, Hou L, Wu Y Tags: Am J Physiol Renal Physiol Source Type: research

Development of glomerular hyperfiltration, a multiphasic phenomenon.
Abstract Trajectory of glomerular filtration rate (GFR) in relation to glomerular hyperfiltration (GHF) has been unknown. It was evaluated retrospectively in GHF-free 23,982 health examinees who were followed for 2 to 10 years (a mean of 5.1 years). GFR was estimated by the serum creatinine concentration and GHFwas defined as age- and sex-specific eGFR ≥ 95% Japanese general population. The temporal profile of eGFR was plotted in the GHF-centered way, which was fitted to random coefficient linear mixed model. Out of the 23,982 subjects, 797 and 23,185 developed and not developed GHF, respectively, so that they ...
Source: Am J Physiol Renal P... - November 2, 2020 Category: Urology & Nephrology Authors: Shimada Y, Nakasone Y, Hirabayashi K, Sakuma T, Koike H, Oguchi T, Yamashita K, Uchimido R, Moriya T, Komatsu M, Aizawa T Tags: Am J Physiol Renal Physiol Source Type: research

Inhibiting 15-PGDH prevents ischemic renal injury by PGE2/EP4 signaling pathway mediating vasodilation, increased renal blood flow, and increased adenosine/A2A.
Abstract We demonstrate the marked activity of SW033291, an inhibitor of 15-hydoxyprostaglandin dehydrogenase (15-PGDH), in preventing acute kidney injury (AKI) in a murine model of ischemia reperfusion injury. AKI due to ischemic injury represents a significant clinical problem. Prostaglandin E2 (PGE2) is vasodilatory in the kidney, but is rapidly degraded in vivo due to catabolism by 15-PGDH. We investigated the potential of SW033291, a potent and specific 15-PGDH inhibitor, as prophylactic treatment for ischemic AKI. Prophylactic administration of SW033291 significantly increased renal tissue PGE2 levels and in...
Source: Am J Physiol Renal P... - November 2, 2020 Category: Urology & Nephrology Authors: Kim HJ, Kim SH, Kim M, Baik H, Park SJ, Kang MS, Kim DH, Kim BW, Markowitz SD, Bae KB Tags: Am J Physiol Renal Physiol Source Type: research

Sex differences in renal mitochondrial function: a hormone-gous opportunity for research.
Abstract Sex differences (biological distinctions between males and females) present a complex interplay of genetic, developmental, biological, and environmental factors. More and more studies are shedding light on importance of sex differences in normal physiology and susceptibility to cancer, cardiovascular and renal conditions, and neurodegenerative diseases. This mini-review is devoted to the role of sex dimorphisms in renal function, with a focus on the distinctions between male and female mitochondria. Here, we cover the aspects of renal mitochondrial bioenergetics where sex differences have been reported to...
Source: Am J Physiol Renal P... - November 2, 2020 Category: Urology & Nephrology Authors: Sultanova R, Schibalski R, Yankelevich IA, Stadler K, Ilatovskaya DV Tags: Am J Physiol Renal Physiol Source Type: research

A Uropathogenic E. coli UTI89 model of prostatic inflammation and collagen accumulation for use in studying aberrant collagen production in the prostate.
Abstract Bacterial infection is one known etiology of prostatic inflammation. Prostatic inflammation is associated with prostatic collagen accumulation and both are linked to progressive lower urinary tract symptoms in men. We characterized a model of prostatic inflammation utilizing transurethral instillations of E. coli UTI89 in C57BL/6J male mice with the goal of determining the optimal instillation conditions, understanding the impact of instillation conditions on urinary physiology, and identifying ideal prostatic lobes and collagen 1a1 prostatic cell types for further analysis. The smallest instillation volu...
Source: Am J Physiol Renal P... - November 2, 2020 Category: Urology & Nephrology Authors: Ruetten H, Sandhu JK, Mueller B, Wang P, Zhang HL, Wegner KA, Cadena MT, Sandhu SK, Abler LL, Zhu J, O'Driscoll CA, Chelgren B, Wang Z, Shen T, Barasch J, Bjorling DE, Vezina CM Tags: Am J Physiol Renal Physiol Source Type: research

NaCl cotransporter activity and magnesium handling by the distal convoluted tubule.
Abstract The genetic disease Gitelman syndrome, knockout mice, and pharmacological blockade with thiazide diuretics have revealed that reduced activity of the NaCl cotransporter (NCC) promotes renal Mg2+ wasting. NCC is expressed along the distal convoluted tubule (DCT), and its activity determines Mg2+ entry into DCT cells through transient receptor potential channel subfamily M, member 6 (TRPM6). Several other genetic forms of hypomagnesemia lower the drive for Mg2+ entry by inhibiting activity of the basolateral Na+-K+-ATPase, and reduced NCC activity may do the same. Lower intracellular Mg2+ may promote furthe...
Source: Am J Physiol Renal P... - November 2, 2020 Category: Urology & Nephrology Authors: Maeoka Y, McCormick JA Tags: Am J Physiol Renal Physiol Source Type: research

AMP-activated protein kinase contributes to cisplatin-induced renal epithelial cell apoptosis and acute kidney injury.
In this study, we demonstrated that cisplatin activates AMPK (Thr172 phosphorylation) in cultured renal tubular epithelial cells in a time-dependent manner, which is associated with p53 phosphorylation. Compound C, a selective AMPK inhibitor, suppressed cisplatin-induced AMPK activation, p53 phosphorylation, Bax induction and caspase 3 activation. Furthermore, silencing AMPK expression by siRNA attenuated cisplatin-induced p53 phosphorylation, Bax induction, and caspase 3 activation. In a mouse model of cisplatin-induced kidney injury, compound C inhibited p53 phosphorylation, Bax expression, caspase 3 activation, and apop...
Source: Am J Physiol Renal P... - October 26, 2020 Category: Urology & Nephrology Authors: Jin X, An C, Jiao B, Safirstein RL, Wang Y Tags: Am J Physiol Renal Physiol Source Type: research

Histone deacetylase 6 inhibition mitigates renal fibrosis by suppressing TGF ß and EGFR signaling pathways in obstructive nephropathy.
In this study, we examined the effect of ricolinostat (ACY-1215), a selective inhibitor of HDAC6, on the development of renal fibrosis in a murine model induced by unilateral ureteral obstruction (UUO). HDAC6 was highly expressed in the kidney following UUO injury, which was coincident with deposition of collagen fibrils and expression of α-smooth muscle actin, fibronectin, and collagen III. Administration of ACY-1215 reduced these fibrotic changes and inhibited UUO-induced expression of transforming growth factor ß1 (TGFß1) and phosphorylation of Smad3, while increasing expression of Smad7. ACY-1215 trea...
Source: Am J Physiol Renal P... - October 26, 2020 Category: Urology & Nephrology Authors: Chen X, Yu C, Hou X, Li J, Li T, Qiu A, Liu N, Zhuang S Tags: Am J Physiol Renal Physiol Source Type: research

Renal lymphatic vessel dynamics.
Abstract Similar to other organs, renal lymphatics remove excess fluid, solutes, and macromolecules from the renal interstitium. Given the kidney's unique role in maintaining body fluid homeostasis, renal lymphatics may be critical in this process. However, little is known regarding the pathways involved in renal lymphatic vessel function and there are no studies on the effects of drugs targeting impaired interstitial clearance, such as diuretics. Using pressure myography, we showed that renal lymphatic collecting vessels are sensitive to changes in transmural pressure and have an optimal range of effective pumpin...
Source: Am J Physiol Renal P... - October 26, 2020 Category: Urology & Nephrology Authors: Shelton EL, Yang HC, Zhong J, Salzman MM, Kon V Tags: Am J Physiol Renal Physiol Source Type: research

Beyond the tubule: Pathogenic variants in LRP2, encoding the megalin receptor, result in glomerular loss and early progressive chronic kidney disease.
In conclusion, megalin dysfunction as present in DB/FOAR syndrome confers an increased risk of progression into chronic kidney disease. PMID: 33103447 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - October 26, 2020 Category: Urology & Nephrology Authors: Charlton JR, Tan W, Daouk G, Teot L, Rosen S, Bennett KM, Cwiek A, Nam S, Emma F, Jouret F, Oliveira JP, Tranebjaerg L, Frykholm C, Mane S, Hildebrandt F, Srivastava T, Storm T, Christensen E, Nielsen R Tags: Am J Physiol Renal Physiol Source Type: research

Am J Physiol Renal Physiol; +37 new citations
37 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: Am J Physiol Renal Physiol These pubmed results were generated on 2020/10/08PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - October 8, 2020 Category: Urology & Nephrology Tags: Report Source Type: research

Global REACH 2018: Renal oxygen delivery is maintained during early acclimatization to 4330 m.
Abstract Early acclimatization to high-altitude is characterized by various respiratory, hematological, and cardiovascular adaptations that serve to restore oxygen delivery to tissue. However, less is understood about renal function and the role of renal oxygen delivery (RDO2) during high-altitude acclimatization. We hypothesized that: 1) RDO2 would be reduced after 12-hours of high-altitude exposure (high-altitude day1) but restored to sea-level values after one-week (high-altitude day7); and 2) RDO2 would be associated with renal reactivity (RR), an index of acid-base compensation at high-altitude. Twenty-four h...
Source: Am J Physiol Renal P... - September 29, 2020 Category: Urology & Nephrology Authors: Steele AR, Tymko MM, Meah VL, Simpson LL, Gasho C, Dawkins TG, Villafuerte FC, Ainslie PN, Stembridge M, Moore JP, Steinback CD Tags: Am J Physiol Renal Physiol Source Type: research

A call to action to evaluate renal functional reserve in COVID-19 patients.
Abstract Coronavirus disease 2019 (COVID-19) poses an unprecedented challenge to world health systems substantially increasing hospitalization and mortality rates in all affected countries. Being primarily a respiratory disease, COVID-19 is mainly associated with pneumonia or minor upper respiratory tract symptoms; however, different organs can sustain considerable (if not terminal) damage because of coronavirus. Acute kidney injury (AKI) is the most common complication of COVID-19-related pneumonia and more than 20% of patients requiring ventilatory support develop renal failure. Additionally, chronic kidney dise...
Source: Am J Physiol Renal P... - September 23, 2020 Category: Urology & Nephrology Authors: Cantaluppi V, Guglielmetti G, Dellepiane S, Marengo M, Mehta R, Ronco C Tags: Am J Physiol Renal Physiol Source Type: research

NON-PURINE SELECTIVE XANTHINE OXIDASE INHIBITOR AMELIORATES GLOMERULAR ENDOTHELIAL INJURY IN InsAkita DIABETIC MICE.
In this study, we investigated the contribution of XO activation on the progression of diabetic nephropathy (DN) in a mouse model using selective XO inhibitors. Male Ins2Akita heterozygous mice were used with wild-type (WT) mice as controls. Akita mice were treated with Topiroxostat (Topi) or vehicle for 4 weeks. Serum uric acid levels were significantly reduced in Akita+Topi compared with Akita+Vehicle mice. The Akita + Topi group had significant reduction in the urinary albumin excretion in comparison with the Akita + Vehicle group. Mesangial expansion, glomerular collagen IV deposition, and glomerular endothelial injury...
Source: Am J Physiol Renal P... - September 20, 2020 Category: Urology & Nephrology Authors: Itano S, Kadoya H, Satoh M, Nakamura T, Murase T, Sasaki T, Kanwar YS, Kashihara N Tags: Am J Physiol Renal Physiol Source Type: research

RNA-seq profiling of microdissected glomeruli identifies potential biomarkers for human IgA nephropathy.
Abstract Few studies have examined gene-expression changes occurring in the glomeruli of immunoglobulin A nephropathy (IgAN) using a sensitive transcriptomic profiling method such as RNA sequencing (RNA-seq). We collected glomeruli from biopsy specimens from IgAN patients with relatively preserved kidney function (eGFR ≥ 60 mL/min/1.73 m2 and urine protein-to-creatinine ratio
Source: Am J Physiol Renal P... - September 20, 2020 Category: Urology & Nephrology Authors: Park S, Yang SH, Jeong CW, Moon KC, Kim DK, Joo KW, Kim YS, Lee JW, Lee H Tags: Am J Physiol Renal Physiol Source Type: research

Regulation of mitochondrial dynamics and energetics in the diabetic renal proximal tubule by the β2-adrenergic receptor agonist formoterol.
Regulation of mitochondrial dynamics and energetics in the diabetic renal proximal tubule by the β2-adrenergic receptor agonist formoterol. Am J Physiol Renal Physiol. 2020 Sep 21;: Authors: Cleveland KH, Brosius FC, Schnellmann RG Abstract Diabetes is a prevalent metabolic disease that contributes to ~50% of all end stage renal diseases (ESRD) and has limited treatment options. We previously demonstrated that the β2-adrenergic receptor (AR) agonist formoterol induced mitochondrial biogenesis and promoted recovery from acute kidney injury. Here, we assessed the effects of formoterol on mitoc...
Source: Am J Physiol Renal P... - September 20, 2020 Category: Urology & Nephrology Authors: Cleveland KH, Brosius FC, Schnellmann RG Tags: Am J Physiol Renal Physiol Source Type: research

METTL3 contributes to renal ischemia-reperfusion injury by regulating Foxd1 methylation.
Abstract To investigate the mechanism of renal ischemia-reperfusion injury (IRI) via the regulation of N6-methyl-adenosine (m6A) and relevant genes, IRI was induced in Sprague Dawley rats and the urine and serum creatinine levels and tissue structure changes were observed. m6A and METTL3 protein levels were assessed via dot blotting and western blotting, respectively. The hypoxia/reoxygenation (H/R) cell model was constructed using NRK-52E cells, and METTL3 protein levels were assessed. METTL3 was inhibited to observe its impact on NRK-52E cell apoptosis and m6A expression in H/R processes. Methylated RNA immunopr...
Source: Am J Physiol Renal P... - September 20, 2020 Category: Urology & Nephrology Authors: Meng F, Liu Y, Chen Q, Ma Q, Gu S, Cui R, Cao R, Zhao M Tags: Am J Physiol Renal Physiol Source Type: research

Mutation of ROR γT reveals a role for Th17 cells in both injury and recovery from renal ischemia reperfusion injury.
Mutation of RORγT reveals a role for Th17 cells in both injury and recovery from renal ischemia reperfusion injury. Am J Physiol Renal Physiol. 2020 Sep 14;: Authors: Mehrotra P, Ullah MM, Collett JA, Myers SL, Dwinell MR, Geurts AM, Basile DP Abstract To investigate Th17 cells in the setting of acute kidney injury (AKI), the master regulator of Th17 cell differentiation, RORγT, was mutated in Lewis rats using CRISPR/Cas9 technology. In response to 40 min bilateral renal I/R, Rorc-/- rats were resistant to injury relative to wild-type Rorc+/+ rats. This protection was associated with inhib...
Source: Am J Physiol Renal P... - September 13, 2020 Category: Urology & Nephrology Authors: Mehrotra P, Ullah MM, Collett JA, Myers SL, Dwinell MR, Geurts AM, Basile DP Tags: Am J Physiol Renal Physiol Source Type: research

Distal Convoluted Tubule Sexual Dimorphism Revealed by Advanced 3D-Imaging.
Abstract The thiazide-sensitive sodium chloride cotransporter (NCC) is more abundant in kidneys of females than of males. Because morphological remodeling of the distal convoluted tubule (DCT) is dependent on NCC activity, it has been generally assumed that there is a corresponding sexual dimorphism in the structure of the DCT, leading to a larger female DCT. Until now, this has never been directly examined. Here, optical clearing techniques were combined with antibody labeling of DCT segment markers, state-of-the-art high-speed volumetric imaging and analysis tools to visualize and quantify DCT morphology in male...
Source: Am J Physiol Renal P... - September 13, 2020 Category: Urology & Nephrology Authors: Tahaei E, Coleman R, Saritas T, Ellison DH, Welling PA Tags: Am J Physiol Renal Physiol Source Type: research

A minireview of pharmacologic strategies used to ameliorate polyuria associated with X-linked nephrogenic diabetes insipidus.
Abstract Nephrogenic diabetes insipidus (NDI) is characterized by renal resistance to the antidiuretic hormone arginine vasopressin (AVP) which leads to polyuria, plasma hyperosmolarity, polydipsia and impaired quality of living. Inherited forms are caused by X-linked loss-of-function mutations in the gene encoding the vasopressin 2- receptor (V2R) or autosomal mutations in the gene encoding aquaporin 2 (AQP2). A common acquired form is lithium-induced NDI. AVP facilitates reabsorption of water through increased abundance and insertion of AQP2 in the apical membrane of the principal cells in the collecting ducts. ...
Source: Am J Physiol Renal P... - September 13, 2020 Category: Urology & Nephrology Authors: Mortensen LA, Bistrup C, Jensen BL, Hinrichs GR Tags: Am J Physiol Renal Physiol Source Type: research

G Protein-coupled Estrogen Receptor as a Novel Regulator of Blood Pressure.
Abstract The mechanisms underlying hypertension are multi-faceted and incompletely understood. New evidence suggests that the G protein-coupled estrogen receptor 1 (GPER1) mediates protective actions within the cardiovascular and renal systems. This minireview focuses on recent advancements in our understanding of the vascular, renal, and cardiac GPER1-mediated mechanisms that influence blood pressure regulation. We emphasize clinical and basic evidence that suggests GPER1 as a novel target to aid therapeutic strategies for hypertension. Furthermore, we discuss current controversies and challenges facing GPER1-rel...
Source: Am J Physiol Renal P... - September 6, 2020 Category: Urology & Nephrology Authors: Gohar EY Tags: Am J Physiol Renal Physiol Source Type: research

A role for the tubular Na+-H+-exchanger NHE3 in the natriuretic effect of the SGLT2 inhibitor empagliflozin.
Abstract Inhibitors of the proximal tubular sodium glucose cotransporter SGLT2 are natriuretic and they lower blood pressure. There are reports that the activities of SGLT2 and the Na+-H+-exchanger, NHE3, are coordinated. If so, then part of the natriuretic response to an SGLT2 inhibitor is mediated by suppressing NHE3. To examine this further, we compared the effects of the SGLT2 inhibitor, empagliflozin, on urine composition and systolic blood pressure (SBP) in non-diabetic mice with tubule-specific NHE3 knock-down (NHE3-ko) and wild-type littermates (WT). A single dose of empagliflozin, titrated to cause minima...
Source: Am J Physiol Renal P... - September 6, 2020 Category: Urology & Nephrology Authors: Onishi A, Fu Y, Patel R, Darshi M, Crespo-Masip M, Huang W, Song P, Freeman B, Kim YC, Soleimani M, Sharma K, Thomson SC, Vallon V Tags: Am J Physiol Renal Physiol Source Type: research

Praliciguat inhibits progression of diabetic nephropathy in ZSF1 rats and suppresses inflammation and apoptosis in human renal proximal tubular cells.
In conclusion, praliciguat improved proteinuria in the ZSF1 rat model of DN, and its actions in human RPTC suggest that tubular effects may contribute to its renal benefits, building upon strong evidence for the role of cGMP signaling in renal health. PMID: 32865013 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - August 30, 2020 Category: Urology & Nephrology Authors: Liu G, Shea CM, Jones JE, Price GM, Warren W, Lonie E, Yan S, Currie MG, Profy AT, Masferrer JL, Zimmer DP Tags: Am J Physiol Renal Physiol Source Type: research

A (pro)renin receptor decoy peptide PRO20 protects against adriamycin-induced nephropathy by targeting intrarenal renin-angiotensin system.
Abstract Adriamycin (ADR) administration in susceptible rodents such as the BALB/c mouse strain produces injury to the glomerulus mimicking human chronic kidney disease (CKD) due to primary focal segmental glomerulosclerosis. The goal of the present study was to use this model to investigate antiproteinuric action of (pro)renin receptor (PRR) decoy inhibitor PRO20. BALB/c mice were pretreated for 1 day with PRO20 at 500 μg/kg/day via an osmotic minipump, followed by a single injection of vehicle or ADR (10 mg/kg) via the tail vein. Albuminuria and renal function were analyzed at 4th week post-ADR administration...
Source: Am J Physiol Renal P... - August 30, 2020 Category: Urology & Nephrology Authors: Luo R, Yang KT, Wang F, Xu C, Yang T Tags: Am J Physiol Renal Physiol Source Type: research

Soluble (pro)renin receptor promotes fibrotic response in renal proximal tubule epithelial cells in vitro via Akt/ β-catenin/Snail signaling pathway.
Soluble (pro)renin receptor promotes fibrotic response in renal proximal tubule epithelial cells in vitro via Akt/β-catenin/Snail signaling pathway. Am J Physiol Renal Physiol. 2020 Aug 31;: Authors: Xie S, Su J, Lu A, Lai Y, Mo S, Pu M, Yang T Abstract Tubulointerstitial fibrosis has been regarded as a critical event in the pathogenesis of chronic kidney disease (CKD). Soluble form of PRR (sPRR), generated by site-1 protease (S1P) cleavage of full-length PRR, is detected in biological fluid and elevated under certain pathological conditions. The present study was designed to evaluate the potenti...
Source: Am J Physiol Renal P... - August 30, 2020 Category: Urology & Nephrology Authors: Xie S, Su J, Lu A, Lai Y, Mo S, Pu M, Yang T Tags: Am J Physiol Renal Physiol Source Type: research

Vitamin K Deficiency: An Emerging Player in the Pathogenesis of Vascular Calcification and an Iatrogenic Consequence of Therapies in Advanced Renal Disease.
Abstract Vascular calcification is a known complication of chronic kidney disease (CKD). The prevalence of vascular calcification in patients with non-dialysis-dependent CKD stages 3-5 has been shown to be as high as 79%. [1] Vascular calcification has been associated with increased risk for mortality, hospital admissions, and cardiovascular disease. [1] [2] [3] [4] Alterations in mineral and bone metabolism play a pivotal role in the pathogenesis of vascular calcification in CKD. As CKD progresses, levels of fibroblast growth factor-23 (FGF-23), parathyroid hormone (PTH) and serum phosphorus increase and 1,25-(OH...
Source: Am J Physiol Renal P... - August 23, 2020 Category: Urology & Nephrology Authors: Levy D, Grewal R, Le TH Tags: Am J Physiol Renal Physiol Source Type: research

Protein Disulfide Isomerase Inhibition Impairs Keap1/Nrf2 Signaling and Mitochondrial Function and Induces Apoptosis in Renal Proximal Tubular Cells.
Abstract Renal proximal tubular apoptosis plays a critical role in kidney health and disease. However, cellular molecules that trigger renal apoptosis remain elusive. Here, we evaluated the effect of inhibiting protein disulfide isomerase (PDI), a critical thioredoxin chaperone protein, on apoptosis, and the underlying mechanisms in human renal proximal tubular (HK2) cells. HK2 cells were transfected with PDI specific siRNA in the absence and presence of an antioxidant tempol. PDI siRNA transfection resulted in a decrease of ~70% in PDI protein expression and enzyme activity. PDI inhibition increased caspase-3 act...
Source: Am J Physiol Renal P... - August 23, 2020 Category: Urology & Nephrology Authors: Pokkunuri ID, Lokhandwala MF, Banday AA Tags: Am J Physiol Renal Physiol Source Type: research

MAD2B contributes to parietal epithelial cell activation and crescentic glomerulonephritis via Skp2.
Abstract Mitotic spindle assembly checkpoint protein 2 (MAD2B), a well-known anaphase-promoting complex/cyclosome (APC/C) inhibitor and a small subunit of DNA polymerase ζ, is critical for mitotic control and DNA repair. Previously, we detected a strong increase of MAD2B in the glomeruli from crescentic glomerulonephritis patients and anti-glomerular basement membrane (anti-GBM) rats, which predominantly originated from activated parietal epithelial cells (PECs). Consistently, in vitro MAD2B was increased in tumor necrosis factor-α (TNF-α)-treated PECs, along with cell activation and proliferation...
Source: Am J Physiol Renal P... - August 23, 2020 Category: Urology & Nephrology Authors: Ye C, Xiong W, Lei CT, Tang H, Su H, Yi F, Zhang C Tags: Am J Physiol Renal Physiol Source Type: research

(Pro)renin receptor promotes crescent formation via the ERK1/2 and Wnt/ β-catenin pathways in glomerulonephritis.
(Pro)renin receptor promotes crescent formation via the ERK1/2 and Wnt/β-catenin pathways in glomerulonephritis. Am J Physiol Renal Physiol. 2020 Aug 24;: Authors: Urushihara M, Kondo S, Kinoshita Y, Ozaki N, Jamba A, Nagai T, Fujioka K, Hattori T, Kagami S Abstract (Pro)renin receptor ((P)RR) has multiple functions, but its regulation and role in the pathogenesis in glomerulonephritis (GN) are poorly defined. The aims of this study were to determine the effects of direct renin inhibition (DRI) and demonstrate the role of (P)RR on the progression of crescentic GN. Anti-glomerular basement membran...
Source: Am J Physiol Renal P... - August 23, 2020 Category: Urology & Nephrology Authors: Urushihara M, Kondo S, Kinoshita Y, Ozaki N, Jamba A, Nagai T, Fujioka K, Hattori T, Kagami S Tags: Am J Physiol Renal Physiol Source Type: research

Expression of Acsm2, a kidney-specific gene, parallels the function and maturation of proximal tubular cells.
In this study, we found that the Acsm2 gene was expressed specifically and at a high level in normal adult kidneys. The expression of Acsm2 in kidneys followed a maturational pattern: it was low in newborn mice and increased with kidney development and maturation. In situ hybridization and immunohistochemistry revealed that Acsm2 was expressed specifically in proximal tubular cells of adult kidneys. Data from the Encyclopedia of DNA Elements database revealed that the Acsm2 gene locus in the mouse has specific histone modifications related to the active transcription of the gene exclusively in kidney cells. Following acute...
Source: Am J Physiol Renal P... - August 23, 2020 Category: Urology & Nephrology Authors: Watanabe H, Paxton RL, Tolerico MR, Nagalakshmi VK, Tanaka S, Okusa MD, Goto S, Narita I, Watanabe S, Sequeira-Lοpez MLS, Gomez RA Tags: Am J Physiol Renal Physiol Source Type: research

Impaired Renal Hemodynamics and Glomerular Hyperfiltration Contribute to Hypertension-Induced Renal Injury.
Abstract Recently, we reported a mutation in γ-Adducin (ADD3) was associated with an impaired myogenic response of the afferent arteriole and hypertension-induced chronic kidney disease (CKD) in FHH rats. However, the mechanisms by which altered renal blood flow (RBF) autoregulation promotes hypertension-induced renal injury remains to be determined. The present study compared the time course of changes in renal hemodynamics and the progression of CKD during the development of DOCA-salt hypertension in FHH 1BN congenic rats (WT) with an intact myogenic response versus FHH 1BN Add3KO (Add3KO) rats which have ...
Source: Am J Physiol Renal P... - August 23, 2020 Category: Urology & Nephrology Authors: Fan L, Gao W, Nguyen BV, Jefferson JR, Liu Y, Fan F, Roman RJ Tags: Am J Physiol Renal Physiol Source Type: research

C57BL/6 mice require a higher dose of cisplatin to induce renal fibrosis and CCL2 correlates with cisplatin-induced kidney injury.
In this study, we demonstrate that increasing the dose of cisplatin to 9 mg/kg once a week for four weeks is sufficient to consistently induce fibrosis in C57BL/6 mice while maintaining animal survival. In addition, we present that cohorts of C57BL/6 mice purchased from Jackson one year apart and mice bred in house display variability in renal outcomes following repeated low dose cisplatin treatment. In depth analyses of this intra-animal variability revealed CCL2 as a marker of cisplatin-induced kidney injury through correlation studies. In addition, significant immune cell infiltration was observed in the kidney after fo...
Source: Am J Physiol Renal P... - August 23, 2020 Category: Urology & Nephrology Authors: Sears SM, Sharp CN, Krueger AM, Oropilla GB, Saforo D, Doll MA, Megyesi J, Beverly LJ, Siskind LJ Tags: Am J Physiol Renal Physiol Source Type: research

Intracellular location of aquaporin-2 serine 269 phosphorylation and dephosphorylation in kidney collecting duct cells.
Abstract Aquaporin-2 (AQP2) is a vasopressin-regulated water channel protein responsible for water reabsorption by the kidney collecting ducts. Under control conditions, most AQP2 resides in the recycling endosomes of the principal cells where it answers to vasopressin with trafficking to the apical plasma membrane to increase water reabsorption. Upon vasopressin withdrawal, apical AQP2 retreats to the early endosomes before joining the recycling endosomes for the next vasopressin stimulation. Prior studies have demonstrated a role of AQP2 S269 phosphorylation in reducing AQP2 endocytosis thereby prolonging apical...
Source: Am J Physiol Renal P... - August 16, 2020 Category: Urology & Nephrology Authors: Wong KY, Wang WL, Su SH, Liu CF, Yu MJ Tags: Am J Physiol Renal Physiol Source Type: research