ArticleAmerican journal of physiology. Renal physiology2012
Peroxisome proliferator-activated receptor-γ agonists repress epithelial sodium channel expression in the kidney.
Article in American journal of physiology. Renal physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- The expanding role of Nogo-B in hypertension: linking kidney physiology, endothelial function and inflammation.Journal of hypertension · 2026Review
- The Many Facets of PPAR-γ Agonism in Obesity and Associated Comorbidities: Benefits, Risks, Challenges, and Future Directions.Current obesity reports · 2025Review
- Cytoarchitectural modifications and antiinflammatory strategies in tendinopathy recovery.PloS one · 2025Article
- PPARG agonist pioglitazone influences diurnal kidney medulla mRNA expression of core clock, inflammation-, and metabolism-related genes disrupted by reverse feeding in mice.Physiological reports · 2022Article
- Role of the Peroxisome Proliferator Activated Receptors in Hypertension.Circulation research · 2021Review
- Peroxisome Proliferator-Activated Receptor γ and Its Role in Adipocyte Homeostasis and Thiazolidinedione-Mediated Insulin Sensitization.Molecular and cellular biology · 2018Article
- PPARγ signaling and emerging opportunities for improved therapeutics.Pharmacological research · 2016Review
- Thiazolidinediones and Edema: Recent Advances in the Pathogenesis of Thiazolidinediones-Induced Renal Sodium Retention.PPAR research · 2015Review
- PPARγ agonist-induced fluid retention depends on αENaC expression in connecting tubules.Nephron · 2015Article
- Tribbles homolog 3 attenuates mammalian target of rapamycin complex-2 signaling and inflammation in the diabetic kidney.Journal of the American Society of Nephrology : JASN · 2014Article
- Diuretics prevent thiazolidinedione-induced cardiac hypertrophy without compromising insulin-sensitizing effects in mice.The American journal of pathology · 2014Article
- Increased susceptibility of db/db mice to rosiglitazone-induced plasma volume expansion: role of dysregulation of renal water transporters.American journal of physiology. Renal physiology · 2013Article
- PPARγ signaling and metabolism: the good, the bad and the future.Nature medicine · 2013Review
- Noninsulin glucose-lowering agents for the treatment of patients on dialysis.Nature reviews. Nephrology · 2013Review
- Thiazolidinedione-induced fluid retention: recent insights into the molecular mechanisms.PPAR research · 2013Article
- Role of renal proximal tubule transport in thiazolidinedione-induced volume expansion.World journal of nephrology · 2012Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Thiazolidinediones (TZDs), known as peroxisome proliferator-activated receptor (PPAR) agonists, are used to treat type 2 diabetes. However, ∼5% of patients experience the treatment-limiting side effect of edema. Studies have implicated activation of the epithelial sodium channel (ENaC) as a cause of TZD-induced fluid retention, although there have been conflicting reports. The goal of this study was to resolve the role of PPARγ in control of ENaC isoforms in the kidney. Herein, we demonstrate in mice that rosiglitazone (RGZ), a PPARγ ligand, increases body weight and abdominal fat pad fluid content and reduces hematocrit. Seven days of RGZ decreases ENaCα and ENaCβ mRNA and ENaCγ protein expression in the kidney cortex, and acute treatment for 5 h with pioglitazone, another potent TZD, does not increase renal ENaC isoform mRNA or protein expression. Pioglitazone also decreases ENaCα and ENaCγ mRNA expression in a cortical collecting duct cell line. As no direct transcriptional studies had been conducted, we examined the PPARγ-dependent regulation of ENaC. Pioglitazone represses ENaCγ promoter activity, and this repression is partially relieved by inhibition of protein synthesis. Chromatin immunoprecipitation assays revealed that repression is associated with a decrease in histone H4K5 acetylation at the proximal ENaCγ promoter. In summary, TZDs do not increase ENaC mRNA expression in the kidney, and in fact repress the ENaCγ promoter via an indirect transcriptional mechanism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.