ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2021
Critical roles of SMYD2 lysine methyltransferase in mediating renal fibroblast activation and kidney fibrosis.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 23 citations in OpenAlex.
- Genetic depletion or pharmacological degradation of EZH2 attenuates renal fibrosis via suppressing Notch signaling.Clinical epigenetics · 2025Article
- Histone methylation of kidney disease: fact or fantasy?Renal failure · 2025Review
- Epigenetic histone modifications in kidney disease and epigenetic memory.Clinical and experimental nephrology · 2025Review
- A Novel Inhibitor of Methyltransferase SMYD2, AZ505 Protects Against Peritoneal Fibrosis in Mice.Clinical and experimental pharmacology & physiology · 2025Article
- SMYD2 Promotes Renal Tubular Cell Apoptosis and Chronic Kidney Disease Following Cisplatin Nephrotoxicity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Histone methyltransferase SMYD2 regulates the activation of hepatic stellate cells by activating TLR4 signaling.Scientific reports · 2025Article
- UHRF1 promotes epithelial-mesenchymal transition mediating renal fibrosis by activating the TGF-β/SMAD signaling pathway.Scientific reports · 2025Article
- Epigenetic Regulation of Ferroptosis in Chronic Kidney Disease: Mechanisms and Implications.Research (Washington, D.C.) · 2025Review
- SMYD family in cancer: epigenetic regulation and molecular mechanisms of cancer proliferation, metastasis, and drug resistance.Experimental & molecular medicine · 2024Review
- SMYD2 Promotes Calcium Oxalate-Induced Glycolysis in Renal Tubular Epithelial Cells via PTEN Methylation.Biomedicines · 2024Article
- Kidney Aging and Chronic Kidney Disease.International journal of molecular sciences · 2024Review
- Epigenetic Regulation of EMP/EMT-Dependent Fibrosis.International journal of molecular sciences · 2024Review
- Kidney fibrosis: from mechanisms to therapeutic medicines.Signal transduction and targeted therapy · 2023Review
- Cross talk between lysine methyltransferase Smyd2 and TGF-β-Smad3 signaling promotes renal fibrosis in autosomal dominant polycystic kidney disease.American journal of physiology. Renal physiology · 2022Article
- Targeting lysine-specific demethylase 1A inhibits renal epithelial-mesenchymal transition and attenuates renal fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Pharmacological inhibition of SMYD2 protects against cisplatin-induced acute kidney injury in mice.Frontiers in pharmacology · 2022Article
- The Role of Histone H3 Methylation in Acute Kidney Injury.Drug design, development and therapy · 2022Review
- Protein Methylation in Diabetic Kidney Disease.Frontiers in medicine · 2022Review
- The Role and Mechanism of Lysine Methyltransferase and Arginine Methyltransferase in Kidney Diseases.Frontiers in pharmacology · 2022Review
- Lysine Methyltransferases SMYD2 and SMYD3: Emerging Targets in Kidney Diseases.Kidney diseases (Basel, Switzerland)Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
SET and MYND domain protein 2 (SMYD2) is a lysine methyltransferase that mediates histone H3 lysine 36 trimethylation (H3K36me3) and acts as a regulator of tumorgenesis and cystic growth. However, its role in renal fibrosis remains unknown. In this study, we found that SMYD2 was highly expressed in the murine kidney of renal fibrosis induced by unilateral ureteral obstruction, and primarily located in interstitial fibroblasts and renal tubular epithelial cells. Pharmacological inhibition of SMYD2 with AZ505, a highly selective inhibitor of SMYD2, protected against renal fibrosis and inhibited activation/proliferation of renal interstitial fibroblasts and conversion of epithelial cells to a profibrotic phenotype in this model. In cultured renal interstitial fibroblasts, treatment with AZ505 or silencing of SMYD2 by specific siRNA also inhibited serum- or TGF-β1-induced activation and proliferation of renal interstitial fibroblasts. Mechanistic studies showed that SMYD2 inhibition reduced phosphorylation of several profibrotic signaling molecules, including Smad3, extracellular signal-regulated kinase 1/2, AKT, signal transducer and activator of transcription-3 and nuclear factor-κB in both injured kidney and cultured renal fibroblasts. AZ505 was also effective in suppressing renal expression of Snail and Twist, two transcriptional factors that mediate renal partial epithelial-mesenchymal transition and fibrosis. Conversely, AZ505 treatment prevented downregulation of Smad7, a renoprotective factor in vivo and in vitro. These results indicate that SMYD2 plays a critical role in mediating conversion of epithelial cells to a profibrotic phenotype, renal fibroblast activation and renal fibrogenesis, and suggest that SMYD2 may be a potential target for the treatment of chronic fibrosis in kidney disease.
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Registered trials
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