ArticleKidney international2015
Smad3 deficiency protects mice from obesity-induced podocyte injury that precedes insulin resistance.
Article in Kidney international, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- Single-cell and high-resolution spatial profiling of podocytopathies reveals core mechanisms of podocyte injury.Science advances · 2026Article
- SETDB2 Mitigates Podocyte Dysfunction in Diabetic Kidney Disease Through Epigenetic Silencing of SMAD3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Fatty acid metabolism: opportunities and challenges of traditional Chinese medicine in the treatment of renal fibrosis.Chinese medicine · 2026Review
- New potential therapeutic targets of metabolic disorder-associated kidney disease and diabetic kidney disease.Kidney international · 2026Review
- CCN5 negatively regulates TGF-β-induced endometriosis associated fibrosis through Wnt/β-catenin signaling via Smad3-dependent mechanism.Journal of translational medicine · 2025Article
- Recent advances in targeting obesity, with a focus on TGF-β signaling and vagus nerve innervation.Bioelectronic medicine · 2025Review
- Palmitate-increased TGF-β1 Gene Expression and p-Smad2/3 Protein Levels Attenuated by Chicoric Acid in Patients with Type 2 Diabetes Mellitus.Reports of biochemistry & molecular biology · 2025Article
- Modulation of TGF-β signaling new approaches toward kidney disease and fibrosis therapy.International journal of biological sciences · 2025Review
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- Review
- Renoprotection by Inhibiting Connexin 43 Expression in a Mouse Model of Obesity-Related Renal Injury.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- Role of miR-379 in high-fat diet-induced kidney injury and dysfunction.American journal of physiology. Renal physiology · 2022Article
- PTEN-induced kinase 1 deficiency alters albumin permeability and insulin signaling in podocytes.Journal of molecular medicine (Berlin, Germany) · 2022Article
- High-calorie diet results in reversible obesity-related glomerulopathy in adult zebrafish regardless of dietary fat.American journal of physiology. Renal physiology · 2022Article
- A human-based multi-gene signature enables quantitative drug repurposing for metabolic disease.eLife · 2022Article
- The Updates of Podocyte Lipid Metabolism in Proteinuric Kidney Disease.Kidney diseases (Basel, Switzerland) · 2021Review
- Pathophysiology of diabetic kidney disease: impact of SGLT2 inhibitors.Nature reviews. Nephrology · 2021Review
- New Pandemic: Obesity and Associated Nephropathy.Frontiers in medicine · 2021Review
- Paclitaxel Ameliorates Palmitate-Induced Injury in Mouse Podocytes.Medical science monitor basic research · 2020Article
- Smad3 signalling affects high glucose-induced podocyte injury via regulation of the cytoskeletal protein transgelin.Nephrology (Carlton, Vic.) · 2020Article
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signaling by TGF-β/Smad3 plays a key role in renal fibrosis. As obesity is one of the major risk factors of chronic and end-stage renal disease, we studied the role of Smad3 signaling in the pathogenesis of obesity-related renal disease. After switching to a high fat diet, the onset of Smad3 C-terminal phosphorylation, increase in albuminuria, and the early stages of peripheral and renal insulin resistance occurred at 1 day, and 4 and 8 weeks, respectively, in C57BL/6 mice. The loss of synaptopodin, a functional marker of podocytes, and phosphorylation of the Smad3 linker region (T179 and S213) appeared after 4 weeks of the high fat diet. This suggests a temporal pattern of Smad3 signaling activation leading to kidney injury and subsequent insulin resistance in the development of obesity-related renal disease. In vivo, Smad3 knockout attenuated the high fat diet-induced proteinuria, renal fibrosis, overall podocyte injury, and mitochondrial dysfunction in podocytes. In vitro palmitate caused a rapid activation of Smad3 in 30 min, loss of synaptopodin in 2 days, and impaired insulin signaling in 3 days in isolated mouse podocytes. Blockade of either Smad3 phosphorylation by SIS3 (a Smad3 inhibitor) or T179 phosphorylation by flavopiridol (a CDK9 inhibitor) prevented the palmitate-induced loss of synaptopodin and mitochondrial function in podocytes. Thus, Smad3 signaling plays essential roles in obesity-related renal disease and may be a novel therapeutic target.
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