ArticleThe Journal of clinical investigation2017
Lysine methyltransferase SMYD2 promotes cyst growth in autosomal dominant polycystic kidney disease.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 3 of them syntheses that pooled it.
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Who cites it
84 citing papers in PubMed, 3 syntheses or guidelines pooled it, 116 citations in OpenAlex.
- The Role of Immune Cells as Modulators of Progression in Polycystic Kidney Disease: A Systematic Review.Kidney360 · 2026Pooled it
- Pooled it
- Differential methylation as a diagnostic biomarker of rare renal diseases: a systematic review.BMC nephrology · 2019Pooled it
- Targeting Runx1 Slows Cyst Growth in Autosomal Dominant Polycystic Kidney Disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- α -Klotho Promotes Cell Death and Suppresses Inflammation through TNF-Cellular Inhibitor of Apoptosis Protein 1 Signaling in Autosomal Dominant Polycystic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2026Article
- Immune microenvironment in autosomal dominant polycystic kidney disease.Genes & diseases · 2026Review
- Chromatin Remodeling in VSMC Phenotype Switching During Vascular Remodeling: From Mechanism to Therapeutic Potential.Biomolecules · 2026Review
- Epithelial Dynamics of Cystogenesis in Genetic Models of Autosomal Dominant Polycystic Kidney Disease.Cells · 2026Article
- Article
- Inflammation in cardiovascular-kidney-metabolic syndrome: key roles and underlying mechanisms-a comprehensive review.Molecular and cellular biochemistry · 2025Review
- Histone methylation of kidney disease: fact or fantasy?Renal failure · 2025Review
- A Novel Inhibitor of Methyltransferase SMYD2, AZ505 Protects Against Peritoneal Fibrosis in Mice.Clinical and experimental pharmacology & physiology · 2025Article
- Role of SMYD2 in gastrointestinal cancer progression (Review).Oncology letters · 2025Review
- 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
- Downregulation of EZH2 Promotes Renal Epithelial Cellular Senescence and Kidney Aging.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
- CRISPR-Cas9 system in autosomal dominant polycystic kidney disease: a comprehensive review.Childhood kidney diseases · 2025Review
- Targeting ferroptosis: novel therapeutic approaches and intervention strategies for kidney diseases.Frontiers in immunology · 2025Review
- Epithelial DPP4 promotes Ang II-driven renal fibrosis by targeting ACE2 activity in the renin-angiotensin system.International journal of biological sciences · 2025Article
- Enzymatic post-translational modifications of proteins in chronic kidney disease: mechanisms, regulation, and clinical significance.Frontiers in pharmacology · 2025Review
24 more citing papers are in PubMed but not listed here.
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7 authors at 2 institutions in 1 country.
Funding
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is driven by mutations in PKD1 and PKD2 genes. Recent work suggests that epigenetic modulation of gene expression and protein function may play a role in ADPKD pathogenesis. In this study, we identified SMYD2, a SET and MYND domain protein with lysine methyltransferase activity, as a regulator of renal cyst growth. SMYD2 was upregulated in renal epithelial cells and tissues from Pkd1-knockout mice as well as in ADPKD patients. SMYD2 deficiency delayed renal cyst growth in postnatal kidneys from Pkd1 mutant mice. Pkd1 and Smyd2 double-knockout mice lived longer than Pkd1-knockout mice. Targeting SMYD2 with its specific inhibitor, AZ505, delayed cyst growth in both early- and later-stage Pkd1 conditional knockout mouse models. SMYD2 carried out its function via methylation and activation of STAT3 and the p65 subunit of NF-κB, leading to increased cystic renal epithelial cell proliferation and survival. We further identified two positive feedback loops that integrate epigenetic regulation and renal inflammation in cyst development: SMYD2/IL-6/STAT3/SMYD2 and SMYD2/TNF-α/NF-κB/SMYD2. These pathways provide mechanisms by which SMYD2 might be induced by cyst fluid IL-6 and TNF-α in ADPKD kidneys. The SMYD2 transcriptional target gene Ptpn13 also linked SMYD2 to other PKD-associated signaling pathways, including ERK, mTOR, and Akt signaling, via PTPN13-mediated phosphorylation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.