ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2020
Identification of histone deacetylase 8 as a novel therapeutic target for renal fibrosis.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Histone modification of endothelial-mesenchymal transition in cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Pooled it
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Selective targeting of cortactin tandem repeat acetylation by human lysine deacetylases.The FEBS journal · 2026Article
- HDAC11 promotes renal fibrosis by induing partial epithelial-mesenchymal transition and G2/M phase arrest in renal epithelial cells.Molecular medicine (Cambridge, Mass.) · 2025Article
- Histone deacetylases and their inhibitors in kidney diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Contribution of histone deacetylases (HDACs) to the regulation of histone and non-histone proteins: implications for fibrotic diseases.BMB reports · 2025Review
- Tissue Fibrosis Decoded via Cellular Senescence: Mechanisms, Treatments, and Emerging Technologies.Aging and disease · 2025Review
- GABP Promotes Mesangial Cell Proliferation and Renal Fibrosis Through GLI1 in Diabetic Nephropathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Impact of Klotho in Cancer: From Development and Progression to Therapeutic Potential.Genes · 2025Review
- Acetylation in renal physiology and pathophysiology.Frontiers in pharmacology · 2025Review
- Enzymatic post-translational modifications of proteins in chronic kidney disease: mechanisms, regulation, and clinical significance.Frontiers in pharmacology · 2025Review
- Arylcarboxamide Derivatives as Promising HDAC8 Inhibitors: An Overview in Light of Structure-activity Relationship and Binding Mode of Interaction Analysis.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025Review
- Inflammation-Induced Klotho Deficiency: A Possible Key Driver of Chronic Kidney Disease Progression.International journal of general medicine · 2025Review
- Propionate and butyrate counteract renal damage and progression to chronic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Article
- Histone Deacetylase (HDAC) Inhibitors as a Novel Therapeutic Option Against Fibrotic and Inflammatory Diseases.Biomolecules · 2024Review
- Pathogenesis and management of renal fibrosis induced by unilateral ureteral obstruction.Kidney research and clinical practice · 2024Article
- Inhibition of HDAC8 mitigates AKI by reducing DNA damage and promoting homologous recombination repair.Journal of cellular and molecular medicine · 2024Article
- Role of Histone Modifications in Kidney Fibrosis.Medicina (Kaunas, Lithuania) · 2024Review
- Epigenetic Regulation of EMP/EMT-Dependent Fibrosis.International journal of molecular sciences · 2024Review
- New insights into the role of Klotho in inflammation and fibrosis: molecular and cellular mechanisms.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Histone deacetylases (HDACs) have been shown to alleviate renal fibrosis, however, the role of individual HDAC isoforms in this process is poorly understood. In this study, we examined the role of HDAC8 in the development of renal fibrosis and partial epithelial-mesenchymal transitions (EMT). In a murine model of renal fibrosis induced by unilateral ureteral obstruction (UUO), HDAC8 was primarily expressed in renal tubular epithelial cells and time-dependently upregulated. This occurred in parallel with the deacetylation of cortactin, a nonhistone substrate of HDAC8, and increased expression of three fibrotic markers: α-smooth muscle actin, collagen 1, and fibronectin. Administration of PCI34051, a highly selective inhibitor of HDAC8, restored acetylation of contactin and reduced expression of those proteins. PCI34051 treatment also reduced the number of renal tubular epithelial cells arrested at the G2/M phase of the cell cycle and suppressed phosphorylation of Smad3, STAT3, β-catenin, and expression of Snail after ureteral obstruction. In contrast, HDAC8 inhibition reversed UUO-induced downregulation of BMP7 and Klotho, two renoprotective proteins. In cultured murine proximal tubular cells, treatment with PCI34051 or specific HDAC8 siRNA was also effective in inhibiting transforming growth factor β1 (TGFβ1)-induced deacetylation of contactin, EMT, phosphorylation of Smad3, STAT3, and β-catenin, upregulation of Snail, and downregulation of BMP7 and Klotho. Collectively, these results suggest that HDAC8 activation is required for the EMT and renal fibrogenesis by activation of multiple profibrotic signaling and transcription factors, and suppression of antifibrotic proteins. Therefore, targeting HDAC8 may be novel therapeutic approach for treatment of renal fibrosis.
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Registered trials
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