ArticleKidney international2024
Hypermethylation leads to the loss of HOXA5, resulting in JAG1 expression and NOTCH signaling contributing to kidney fibrosis.
Article in Kidney international, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 33 citations in OpenAlex.
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Quercetin Alleviates Ferroptosis-Induced Renal Fibrosis by Modulating the PRDM9/HMOX1/PTGS2 Axis.ACS omega · 2026Article
- RaFiST: a radiomics model for non-invasive stratification of tumor fibrosis and prognostic prediction in non-small cell lung cancer.European radiology · 2026Article
- Targeting DNA methylation: molecular and in vivo evidence for quinoa and chia nanocapsules as epigenetic modulators in DMBA-treated rats.NPJ science of food · 2026Article
- Transition from acute kidney injury to chronic kidney disease: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Review
- Construction of a DNA Methylation Map of Argali Hybrid Sheep During Mo Infection.Microorganisms · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- The role of histone methylation in fibrosis and its therapeutic potential.Journal of translational medicine · 2026Review
- HOXA5 Suppresses NEK7-Mediated Alveolar Epithelial Pyroptosis in Acute Lung Injury by Transcriptionally Inhibiting KAT2A.The Kaohsiung journal of medical sciences · 2026Article
- DUSP26 protects against acute kidney injury by dephosphorylating p53 at serine 312.Nature communications · 2026Article
- The glycolytic enzyme PFKM promotes renal fibrosis by activating the NF-κB pathway via lactate-mediated H3K18 lactylation.Cellular and molecular life sciences : CMLS · 2026Article
- HNF4A P2 isoform alleviates kidney fibrosis by inhibiting dedifferentiation of proximal tubular cells through JAG1/NOTCH signaling.Cellular & molecular biology letters · 2026Article
- Dissecting the role of epigenetic regulation in oral squamous cell carcinoma microenvironment: mechanisms and therapeutics.Frontiers in immunology · 2026Review
- Review
- HOXA2 exerts anti-renal fibrosis effects through reducing endoplasmic reticulum stress via the upregulation of SIRT1.Communications biology · 2025Article
- Emerging epigenetic modifications in renal fibrosis: From mechanisms to treatments.Acta pharmaceutica Sinica. B · 2025Review
- Mechanotransduction-Epigenetic Coupling in Pulmonary Regeneration: Multifunctional Bioscaffolds as Emerging Tools.Pharmaceuticals (Basel, Switzerland) · 2025Review
- HOX and MEINOX in cellular plasticity, fibrosis, and cancer.World journal of stem cells · 2025Review
- Fibroblast activation and heterogeneity in fibrotic disease.Nature reviews. Nephrology · 2025Review
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Epigenetic regulations, including DNA methylation, are critical to the development and progression of kidney fibrosis, but the underlying mechanisms remain elusive. Here, we show that fibrosis of the mouse kidney was associated with the induction of DNA methyltransferases and increases in global DNA methylation and was alleviated by the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza). Genome-wide analysis demonstrated the hypermethylation of 94 genes in mouse unilateral ureteral obstruction kidneys, which was markedly reduced by 5-Aza. Among these genes, Hoxa5 was hypermethylated at its gene promoter, and this hypermethylation was associated with reduced HOXA5 expression in fibrotic mouse kidneys after ureteral obstruction or unilateral ischemia-reperfusion injury. 5-Aza prevented Hoxa5 hypermethylation, restored HOXA5 expression, and suppressed kidney fibrosis. Downregulation of HOXA5 was verified in human kidney biopsies from patients with chronic kidney disease and correlated with the increased kidney fibrosis and DNA methylation. Kidney fibrosis was aggravated by conditional knockout of Hoxa5 and alleviated by conditional knockin of Hoxa5 in kidney proximal tubules of mice. Mechanistically, we found that HOXA5 repressed Jag1 transcription by directly binding to its gene promoter, resulting in the suppression of JAG1-NOTCH signaling during kidney fibrosis. Thus, our results indicate that loss of HOXA5 via DNA methylation contributes to fibrogenesis in kidney diseases by inducing JAG1 and consequent activation of the NOTCH signaling pathway.
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