Bidirectional relation between dipeptidyl peptidase 4 and angiotensin II type I receptor signaling
Am J Physiol Cell Physiol. 2024 Apr 1;326(4):C1203-C1211. doi: 10.1152/ajpcell.00734.2023. Epub 2024 Mar 4.ABSTRACTCardiometabolic diseases are often associated with heightened levels of angiotensin II (Ang II), which accounts for the observed oxidative stress, inflammation, and fibrosis. Accumulating evidence indicates a parallel upregulation of dipeptidyl dipeptidase 4 (DPP4) activity in cardiometabolic diseases, with its inhibition shown to mitigate oxidative stress, inflammation, and fibrosis. These findings highlight an overlap between the pathophysiological mechanisms used by Ang II and DPP4. Recent evidence demonstr...
Source: American Journal of Physiology. Cell Physiology - April 6, 2024 Category: Cytology Authors: Flavia L Martins Joao Carlos Ribeiro-Silva Ravi Nistala Adriana C C Girardi Source Type: research

Distinct subpopulations of human subcutaneous adipose tissue precursor cells revealed by single-cell RNA sequencing
Am J Physiol Cell Physiol. 2024 Apr 1;326(4):C1248-C1261. doi: 10.1152/ajpcell.00726.2023. Epub 2024 Mar 4.ABSTRACTAdipose-derived stem cells (ADSCs) play an important role in the differential capacity for excess energy storage between upper body abdominal (ABD) adipose tissue (AT) and lower body gluteofemoral (GF) AT. We cultured ADSCs from subcutaneous ABD AT and GF AT isolated from eight women with differential body fat distribution and performed single-cell RNA sequencing. Six populations of ADSCs were identified and segregated according to their anatomical origin. The three ADSC subpopulations in GF AT were characteri...
Source: American Journal of Physiology. Cell Physiology - April 6, 2024 Category: Cytology Authors: Adeline Divoux Katie L Whytock Laszlo Halasz Meghan E Hopf Lauren M Sparks Timothy F Osborne Steven R Smith Source Type: research

Extracellular glucose and dysfunctional insulin receptor signaling independently upregulate arterial smooth muscle TMEM16A expression
Am J Physiol Cell Physiol. 2024 Apr 1;326(4):C1237-C1247. doi: 10.1152/ajpcell.00555.2023. Epub 2024 Mar 4.ABSTRACTDiabetes alters the function of ion channels responsible for regulating arterial smooth muscle membrane potential, resulting in vasoconstriction. Our prior research demonstrated an elevation of TMEM16A in diabetic arteries. Here, we explored the mechanisms involved in Transmembrane protein 16A (TMEM16A) gene expression. Our data indicate that a Snail-mediated repressor complex regulates arterial TMEM16A gene transcription. Snail expression was reduced in diabetic arteries while TMEM16A expression was upregulat...
Source: American Journal of Physiology. Cell Physiology - April 6, 2024 Category: Cytology Authors: Somasundaram Raghavan Masuma Akter Brishti Angelica Bernardelli Alejandro Mata-Daboin Jonathan H Jaggar M Dennis Leo Source Type: research

Dispase/collagenase cocktail allows for coisolation of satellite cells and fibroadipogenic progenitors from human skeletal muscle
This study demonstrates robust isolation of both SCs and FAPs from the same muscle sample with SC recovery more than two times higher than previously reported, which could enable translational studies for muscle injuries.NEW & NOTEWORTHY We demonstrated that a dispase/collagenase cocktail allows for simultaneous isolation of SCs and FAPs with 2× higher SC yield compared with other studies. We provide a thorough characterization of SC and FAP in vitro expansion that other studies have not reported. Following our dissociation, SCs and FAPs were able to expand by up to 1012 cells before reaching senescence and maintained...
Source: American Journal of Physiology. Cell Physiology - April 6, 2024 Category: Cytology Authors: Alis Balayan Marie DeBoutray Thomas G Molley Severin Ruoss Matthew Maceda Ashley Sevier Catherine M Robertson Samuel R Ward Adam J Engler Source Type: research

Coculture with Colon-26 cancer cells decreases the protein synthesis rate and shifts energy metabolism towards glycolysis dominance in C2C12 myotubes
In this study, we investigated the direct effects of Colon-26 cancer cells on the molecular regulating machinery of muscle mass and its bioenergetics using a coculture system with C2C12 myotubes. Our results demonstrated that coculture with Colon-26 cells induced myotube atrophy and reduced skeletal muscle protein synthesis and its regulating mammalian target of rapamycin complex 1 signal transduction. However, we did not observe any activating effects on protein degradation pathways including ubiquitin-proteasome and autophagy-lysosome systems. From a bioenergetic perspective, coculture with Colon-26 cells decreased the C...
Source: American Journal of Physiology. Cell Physiology - April 1, 2024 Category: Cytology Authors: Yuki Tamura Karina Kouzaki Takaya Kotani Koichi Nakazato Source Type: research

A digoxin derivative that potently reduces intraocular pressure - efficacy and mechanism of action in different animal models
Am J Physiol Cell Physiol. 2024 Apr 1. doi: 10.1152/ajpcell.00617.2023. Online ahead of print.ABSTRACTGlaucoma is a blinding disease. Reduction of intraocular pressure (IOP) is the mainstay of treatment, but current drugs show side-effects or become progressively ineffective, highlighting the need for novel compounds. We have synthesized a family of perhydro-1,4-oxazepine derivatives of digoxin, the selective inhibitor of Na,K-ATPase. The cyclobutyl derivative (DcB) displays strong selectivity for the human a2 isoform and potently reduces IOP in rabbits. These observations appeared consistent with a hypothesis that in cili...
Source: American Journal of Physiology. Cell Physiology - April 1, 2024 Category: Cytology Authors: Veluchamy Amutha Barathi Adriana Katz Shashikant Chaudhary Hoi-Lam Li Daniel M Tal Arie L Marcovich Chi-Wai Do Steven J D Karlish Source Type: research

β-adrenergic signaling drives structural and functional maturation of mouse cardiomyocytes
Am J Physiol Cell Physiol. 2024 Apr 1. doi: 10.1152/ajpcell.00426.2023. Online ahead of print.ABSTRACTCardiac maturation represents the last phase of heart development and is characterized by morphofunctional alterations that optimize the heart for efficient pumping. Its understanding provides important insights into cardiac regeneration therapies. Recent evidence implies that adrenergic signals are involved in the regulation of cardiac maturation, but the mechanistic underpinnings involved in this process are poorly understood. Herein, we explored the role of β-adrenergic receptor (β-AR) activation in determining struct...
Source: American Journal of Physiology. Cell Physiology - April 1, 2024 Category: Cytology Authors: Marcos Eliezeck Itamar Couto Guedes Jesus Sergio A Scalzo Bruno de Lima Sanches Kaoma S C Silva Mateus Costa Thassio Mesquita Cibele Rocha-Resende Raphael E Szawka Silvia Guatimosim Source Type: research

Renal upregulation of NCC counteracts empagliflozin-mediated NHE3 inhibition in normotensive but not in hypertensive male rats
This study examined the effect of empagliflozin (EMPA) on renal tubular sodium transport in normotensive and spontaneously hypertensive rats (SHRs). It also tested the hypothesis that EMPA-mediated PT NHE3 inhibition in normotensive rats is associated with upregulation of distal nephron apical sodium transporters. EMPA administration for 14 days reduced BP in 12-week-old SHRs but not in age-matched Wistar rats. PT NHE3 activity was inhibited by EMPA treatment in both Wistar and SHRs. In Wistar rats, EMPA increased NCC activity, mRNA expression, protein abundance, and phosphorylation levels, but not in SHRs. SHRs showed hig...
Source: American Journal of Physiology. Cell Physiology - April 1, 2024 Category: Cytology Authors: Paulo C Castro Thiago Matheus Santos-Rios Fl ávia Letícia Martins Renato O Crajoinas Marcos Vin ícius Caetano Luc ília M A Lessa Weverton Machado Luchi James A McCormick Adriana C C Girardi Source Type: research

BEST4 < sup > + < /sup > cells in the intestinal epithelium
Am J Physiol Cell Physiol. 2024 Apr 1. doi: 10.1152/ajpcell.00042.2024. Online ahead of print.ABSTRACTThe recent development of single cell transcriptomics highlighted the existence of a new lineage of mature absorptive cells in the human intestinal epithelium. This subpopulation is characterized by the specific expression of Bestrophin 4 (BEST4) and of other marker genes including OTOP2, CA7, GUCA2A, GUCA2B, and SPIB. BEST4+ cells appear early in development and are present in all regions of the small and large intestine at a low abundance (<5% of all epithelial cells). Location-specific gene expression profiles in BES...
Source: American Journal of Physiology. Cell Physiology - April 1, 2024 Category: Cytology Authors: Tania Malonga Nathalie Vialaneix Martin Beaumont Source Type: research

Coculture with Colon-26 cancer cells decreases the protein synthesis rate and shifts energy metabolism towards glycolysis dominance in C2C12 myotubes
In this study, we investigated the direct effects of Colon-26 cancer cells on the molecular regulating machinery of muscle mass and its bioenergetics using a coculture system with C2C12 myotubes. Our results demonstrated that coculture with Colon-26 cells induced myotube atrophy and reduced skeletal muscle protein synthesis and its regulating mammalian target of rapamycin complex 1 signal transduction. However, we did not observe any activating effects on protein degradation pathways including ubiquitin-proteasome and autophagy-lysosome systems. From a bioenergetic perspective, coculture with Colon-26 cells decreased the C...
Source: American Journal of Physiology. Cell Physiology - April 1, 2024 Category: Cytology Authors: Yuki Tamura Karina Kouzaki Takaya Kotani Koichi Nakazato Source Type: research

A digoxin derivative that potently reduces intraocular pressure - efficacy and mechanism of action in different animal models
Am J Physiol Cell Physiol. 2024 Apr 1. doi: 10.1152/ajpcell.00617.2023. Online ahead of print.ABSTRACTGlaucoma is a blinding disease. Reduction of intraocular pressure (IOP) is the mainstay of treatment, but current drugs show side-effects or become progressively ineffective, highlighting the need for novel compounds. We have synthesized a family of perhydro-1,4-oxazepine derivatives of digoxin, the selective inhibitor of Na,K-ATPase. The cyclobutyl derivative (DcB) displays strong selectivity for the human a2 isoform and potently reduces IOP in rabbits. These observations appeared consistent with a hypothesis that in cili...
Source: American Journal of Physiology. Cell Physiology - April 1, 2024 Category: Cytology Authors: Veluchamy Amutha Barathi Adriana Katz Shashikant Chaudhary Hoi-Lam Li Daniel M Tal Arie L Marcovich Chi-Wai Do Steven J D Karlish Source Type: research

β-adrenergic signaling drives structural and functional maturation of mouse cardiomyocytes
Am J Physiol Cell Physiol. 2024 Apr 1. doi: 10.1152/ajpcell.00426.2023. Online ahead of print.ABSTRACTCardiac maturation represents the last phase of heart development and is characterized by morphofunctional alterations that optimize the heart for efficient pumping. Its understanding provides important insights into cardiac regeneration therapies. Recent evidence implies that adrenergic signals are involved in the regulation of cardiac maturation, but the mechanistic underpinnings involved in this process are poorly understood. Herein, we explored the role of β-adrenergic receptor (β-AR) activation in determining struct...
Source: American Journal of Physiology. Cell Physiology - April 1, 2024 Category: Cytology Authors: Marcos Eliezeck Itamar Couto Guedes Jesus Sergio A Scalzo Bruno de Lima Sanches Kaoma S C Silva Mateus Costa Thassio Mesquita Cibele Rocha-Resende Raphael E Szawka Silvia Guatimosim Source Type: research

Renal upregulation of NCC counteracts empagliflozin-mediated NHE3 inhibition in normotensive but not in hypertensive male rats
This study examined the effect of empagliflozin (EMPA) on renal tubular sodium transport in normotensive and spontaneously hypertensive rats (SHRs). It also tested the hypothesis that EMPA-mediated PT NHE3 inhibition in normotensive rats is associated with upregulation of distal nephron apical sodium transporters. EMPA administration for 14 days reduced BP in 12-week-old SHRs but not in age-matched Wistar rats. PT NHE3 activity was inhibited by EMPA treatment in both Wistar and SHRs. In Wistar rats, EMPA increased NCC activity, mRNA expression, protein abundance, and phosphorylation levels, but not in SHRs. SHRs showed hig...
Source: American Journal of Physiology. Cell Physiology - April 1, 2024 Category: Cytology Authors: Paulo C Castro Thiago Matheus Santos-Rios Fl ávia Letícia Martins Renato O Crajoinas Marcos Vin ícius Caetano Luc ília M A Lessa Weverton Machado Luchi James A McCormick Adriana C C Girardi Source Type: research

BEST4 < sup > + < /sup > cells in the intestinal epithelium
Am J Physiol Cell Physiol. 2024 Apr 1. doi: 10.1152/ajpcell.00042.2024. Online ahead of print.ABSTRACTThe recent development of single cell transcriptomics highlighted the existence of a new lineage of mature absorptive cells in the human intestinal epithelium. This subpopulation is characterized by the specific expression of Bestrophin 4 (BEST4) and of other marker genes including OTOP2, CA7, GUCA2A, GUCA2B, and SPIB. BEST4+ cells appear early in development and are present in all regions of the small and large intestine at a low abundance (<5% of all epithelial cells). Location-specific gene expression profiles in BES...
Source: American Journal of Physiology. Cell Physiology - April 1, 2024 Category: Cytology Authors: Tania Malonga Nathalie Vialaneix Martin Beaumont Source Type: research

Coculture with Colon-26 cancer cells decreases the protein synthesis rate and shifts energy metabolism towards glycolysis dominance in C2C12 myotubes
In this study, we investigated the direct effects of Colon-26 cancer cells on the molecular regulating machinery of muscle mass and its bioenergetics using a coculture system with C2C12 myotubes. Our results demonstrated that coculture with Colon-26 cells induced myotube atrophy and reduced skeletal muscle protein synthesis and its regulating mammalian target of rapamycin complex 1 signal transduction. However, we did not observe any activating effects on protein degradation pathways including ubiquitin-proteasome and autophagy-lysosome systems. From a bioenergetic perspective, coculture with Colon-26 cells decreased the C...
Source: American Journal of Physiology. Cell Physiology - April 1, 2024 Category: Cytology Authors: Yuki Tamura Karina Kouzaki Takaya Kotani Koichi Nakazato Source Type: research