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 53 papers.
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53 citing papers in PubMed, 57 citations in OpenAlex.
- A review of the sirtuins family: pivotal regulators and emerging therapeutic targets in renal fibrosis.Renal failure · 2026Review
- 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
- Combination of B-cell-guided rituximab and low-dose tacrolimus for primary membranous nephropathy: a retrospective cohort study.Frontiers in medicine · 2026Article
- Comparison of the efficacy of low, moderate and standard doses of rituximab in the treatment of membranous nephropathy.Frontiers in medicine · 2026Article
- Microbiota-gut-kidney axis in health and renal disease.International journal of biological sciences · 2026Review
- The overlap of ANCA associated vasculitis with Sjögren's syndrome in elderly male patient: a case report and literature review.Frontiers in medicine · 2026Article
- Gut microbial-derived metabolites: key players in kidney disease and renal fibrosis.International journal of biological sciences · 2026Review
- Mechanistic elucidation of Wuling Powder targeting macrophage polarization to ameliorate renal ischemia-reperfusion injury via multidimensional computational systems pharmacology coupled with experimental validation.Frontiers in pharmacology · 2026Article
- Identification of biomarkers for chronic renal fibrosis and their relationship with immune infiltration and cell death.Renal failure · 2025Article
- Modified Huangqi Chifeng decoction alleviates podocyte injury on rat with experimental membranous nephropathy.Renal failure · 2025Article
- Acteoside-containing caffeic acid is bioactive functional group of antifibrotic effect by suppressing inflammation via inhibiting AHR nuclear translocation in chronic kidney disease.Acta pharmacologica Sinica · 2025Article
- Mechanisms and Therapeutic Perspectives of Podocyte Aging in Podocytopathies.International journal of molecular sciences · 2025Review
- Laboratory, Clinical, and Pathohistological Significance of the Outcomes of Patients with Membranous Nephropathy After 10 Year of Follow-Up.Life (Basel, Switzerland) · 2025Article
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Authors and funding
8 authors at 6 institutions in 2 countries.
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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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