ArticleActa pharmacologica Sinica2024
Sirtuin 6 protects against podocyte injury by blocking the renin-angiotensin system by inhibiting the Wnt1/β-catenin pathway.
Article in Acta pharmacologica Sinica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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64 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Effects of hypoxia-inducible factor prolyl hydroxylase inhibitors on transfusion and intravenous iron use in chronic kidney disease anemia: a systematic review and meta-analysis.Frontiers in pharmacology · 2026Pooled it
- A review of the sirtuins family: pivotal regulators and emerging therapeutic targets in renal fibrosis.Renal failure · 2026Review
- Association of Chuanhuang Patent Formula with prognosis in patients with acute kidney injury on chronic kidney disease: a retrospective cohort study.Renal failure · 2026Article
- Sodium Butyrate Attenuates Renal Fibrosis by Regulating Glycolysis and Histone H4K12 Lactylation in Diabetic Kidney Disease.Diabetes, obesity & metabolism · 2026Article
- Natural product therapy in diabetic kidney disease: emerging multiomics-mediated signalling pathway and molecular target.Chinese medicine · 2026Review
- Unveiling the mechanism of metabolites derived from gut microbiota in the treatment of acute kidney injury via network pharmacology and bioinformatics.Bioresources and bioprocessing · 2026Article
- Indoxyl Sulfate Promotes Vascular Calcification in Association with Oxidative Stress and Activation of ERK and Wnt/β-Catenin Signaling Pathways.International journal of molecular sciences · 2026Article
- Associations of Physical Activity With Mortality Across Cardiovascular-Kidney-Metabolic Syndrome Stages: Evidence From NHANES 1999 to 2018.Journal of the American Heart Association · 2026Article
- Animal models of idiopathic membranous nephropathy: Recent advances and future perspectives.Animal models and experimental medicine · 2026Review
- Unveiling the therapeutic potential of gut microbiota metabolites for the treatment of renal fibrosis based on network pharmacology study.Bioresources and bioprocessing · 2026Article
- Gastrodin as a nephroprotective agent: Molecular docking-based modulation of oxidative stress, fibrosis, and inflammation.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Review
- Ureic clearance granule ameliorates chronic kidney disease by reshaping microbial dysbiosis via modulating bile acid metabolism.Chinese medicine · 2026Article
- Targeting Oxidative Stress and Inflammation in Pembrolizumab-Induced Renal Injury: A Comparative Evaluation of the Protective Effects of Flunarizine and Carvacrol in Rats.Biomolecules · 2026Article
- Renal fibrosis is induced by hyperactive Wnt/β-catenin pathway via microbial-mediated tryptophan metabolism-driven AhR signaling in rodents and humans.Cellular and molecular life sciences : CMLS · 2026Article
- Hypertension-Induced Renal Injury: From Pathophysiology to Therapeutic Perspectives.Biomedicines · 2026Review
- Sirt6 promotes tumor growth and suppresses immune surveillance.Cancer cell international · 2026Article
- Gut microbial-derived metabolites: key players in kidney disease and renal fibrosis.International journal of biological sciences · 2026Review
- Integrative computational approach to elucidate the efficacy of cordyceps in managing lupus nephritis: from molecular targets to clinical applications.Frontiers in medicine · 2026Article
- Review
- Wnt/β-Catenin Signaling in Diabetic Complications: Mechanisms and Therapeutic Potential.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
4 more citing papers are in PubMed but not listed here.
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8 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sirtuins (Sirts) are a family of nicotinamide adenine dinucleotide-dependent protein deacetylases that share diverse cellular functions. Increasing evidence shows that Sirts play a critical role in podocyte injury, which is a major determinant of proteinuria-associated renal disease. Membranous nephropathy (MN) is a typical glomerular disease in which podocyte damage mediates proteinuria development. In this study we investigated the molecular mechanisms underlying the regulatory roles of Sirt in podocyte injury in MN patients, rats with cationic bovine serum albumin (CBSA)-induced MN and zymosan activation serum (ZAS)-stimulated podocytes. Compared with healthy controls, MN patients showed significant reduction in intrarenal Sirt1 and Sirt6 protein expression. In CBSA-induced MN rats, significant reduction in intrarenal Sirt1, Sirt3 and Sirt6 protein expression was observed. However, only significant decrease in Sirt6 protein expression was found in ZAS-stimulated podocytes. MN patients showed significantly upregulated protein expression of Wnt1 and β-catenin and renin-angiotensin system (RAS) components in glomeruli. CBSA-induced MN rats exhibited significantly upregulated protein expression of intrarenal Wnt1 and β-catenin and their downstream gene products as well as RAS components. Similar results were observed in ZAS-stimulated podocytes. In ZAS-stimulated podocytes, treatment with a specific Sirt6 activator UBCS039 preserved the protein expression of podocin, nephrin and podocalyxin, accompanied by significant inhibition of the protein expression of β-catenin and its downstream gene products, including Snail1 and Twist; treatment with a β-catenin inhibitor ICG-001 significantly preserved the expression of podocyte-specific proteins and inhibited the upregulation of downstream β-catenin gene products accompanied by significant suppression of the protein expression of RAS components. Thus, we demonstrate that Sirt6 ameliorates podocyte injury by blocking RAS signalling via the Wnt1/β-catenin pathway. Sirt6 is a specific therapeutic target for the treatment of podocyte damage-associated renal disease.
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