ArticleJournal of the American Society of Nephrology : JASN2015
Sirtuin1 Maintains Actin Cytoskeleton by Deacetylation of Cortactin in Injured Podocytes.
Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 71 citations in OpenAlex.
- Selective targeting of cortactin tandem repeat acetylation by human lysine deacetylases.The FEBS journal · 2026Article
- Podocyte-related biomarkers' role in evaluating renal toxic effects of silver nanoparticles with the possible ameliorative role of resveratrol in adult male albino rats.Toxicology reports · 2025Article
- Research Progress on Podocyte Pyroptosis in Diabetic Nephropathy.Current medicinal chemistry · 2025Review
- Targeting ferroptosis: novel therapeutic approaches and intervention strategies for kidney diseases.Frontiers in immunology · 2025Review
- Wenyang Jiedu Tongluo formula ameliorates diabetic kidney disease by regulating JAML/SIRT1 signaling to improve lipid metabolism in db/db mice.Frontiers in pharmacology · 2025Article
- Organelle communication maintains mitochondrial and endosomal homeostasis during podocyte lipotoxicity.JCI insight · 2024Article
- ADNP dysregulates methylation and mitochondrial gene expression in the cerebellum of a Helsmoortel-Van der Aa syndrome autopsy case.Acta neuropathologica communications · 2024Article
- Sirtuins in kidney diseases: potential mechanism and therapeutic targets.Cell communication and signaling : CCS · 2024Review
- Sirtuins in kidney homeostasis and disease: where are we now?Frontiers in endocrinology · 2024Review
- Insight into the Molecular Mechanism of Diabetic Kidney Disease and the Role of Metformin in Its Pathogenesis.International journal of molecular sciences · 2023Review
- Novel Role of the SIRT1 in Endocrine and Metabolic Diseases.International journal of biological sciences · 2023Review
- Sirt1 Regulates Corneal Epithelial Migration by Deacetylating Cortactin.Investigative ophthalmology & visual science · 2022Article
- Activation of SIRT1 promotes membrane resealing via cortactin.Scientific reports · 2022Article
- Review
- Review
- SIRT1 Alleviates Aldosterone-Induced Podocyte Injury by Suppressing Mitochondrial Dysfunction and NLRP3 Inflammasome Activation.Kidney diseases (Basel, Switzerland) · 2021Article
- Unraveling the epigenetic landscape of glomerular cells in kidney disease.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Lysine acetylation of cytoskeletal proteins: Emergence of an actin code.The Journal of cell biology · 2020Review
- Decreased Urinary Levels ofInternational journal of molecular sciences · 2020Article
- Histone Deacetylases Take Center Stage on Regulation of Podocyte Function.Kidney diseases (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies have highlighted the renoprotective effect of sirtuin1 (SIRT1), a deacetylase that contributes to cellular regulation. However, the pathophysiologic role of SIRT1 in podocytes remains unclear. Here, we investigated the function of SIRT1 in podocytes. We first established podocyte-specific Sirt1 knockout (SIRT1(pod-/-)) mice. We then induced glomerular disease by nephrotoxic serum injection. The increase in urinary albumin excretion and BUN and the severity of glomerular injury were all significantly greater in SIRT1(pod-/-) mice than in wild-type mice. Western blot analysis and immunofluorescence showed a significant decrease in podocyte-specific proteins in SIRT1(pod-/-) mice, and electron microscopy showed marked exacerbation of podocyte injury, including actin cytoskeleton derangement in SIRT1(pod-/-) mice compared with wild-type mice. Protamine sulfate-induced podocyte injury was also exacerbated by podocyte-specific SIRT1 deficiency. In vitro, actin cytoskeleton derangement in H2O2-treated podocytes became prominent when the cells were pretreated with SIRT1 inhibitors. Conversely, this H2O2-induced derangement was ameliorated by SIRT1 activation. Furthermore, SIRT1 activation deacetylated the actin-binding and -polymerizing protein cortactin in the nucleus and facilitated deacetylated cortactin localization in the cytoplasm. Cortactin knockdown or inhibition of the nuclear export of cortactin induced actin cytoskeleton derangement and dissociation of cortactin from F-actin, suggesting the necessity of cytoplasmic cortactin for maintenance of the actin cytoskeleton. Taken together, these findings indicate that SIRT1 protects podocytes and prevents glomerular injury by deacetylating cortactin and thereby, maintaining actin cytoskeleton integrity.
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