ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025
Hypermethylation and suppression of microRNA219a-2 activates the ALDH1L2/GSH/PAI-1 pathway for fibronectin degradation in renal fibrosis.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed.
- Glycolytic lactylation modulates cell death decisions in diabetic kidney disease: Metabolic‑epigenetic interplay between ferroptosis and autophagy in fibrotic remodeling (Review).International journal of molecular medicine · 2026Review
- Review
- Emerging epigenetic modifications in renal fibrosis: From mechanisms to treatments.Acta pharmaceutica Sinica. B · 2025Review
- The Role of DNA Methyltransferases in Urinary System Diseases.Cancer innovation · 2025Review
- Decoding the ceRNA regulatory landscape: a comprehensive transcriptomic analysis of ncRNA-driven bladder fibrosis following spinal cord injury.Translational andrology and urology · 2025Article
- Investigating potential biomarkers associated with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis using Mendelian randomization and transcriptomic analysis.Arthritis research & therapy · 2025Article
- Beyond Blood Pressure: Emerging Pathways and Precision Approaches in Hypertension-Induced Kidney Damage.International journal of molecular sciences · 2025Review
- Renal tubular epithelial IGFBP7 interacts with PKM2 to drive renal lipid accumulation and fibrosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- RasGRP4 Exacerbates Diabetic Kidney Fibrosis via Aloxe3-Mediated Oxidative Stress and Scar-Associated Macrophage Activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Novel epigenetic cross-talk down-regulates kidney fibrosis after injury.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
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Abstract
Epigenetic regulations, such as DNA methylation and microRNAs, play an important role in renal fibrosis. Here, we report the regulation of microRNA219a-2 by DNA methylation in fibrotic kidneys, unveiling the crosstalk between these epigenetic mechanisms. Through genome-wide DNA methylation analysis and pyrosequencing, we detected the hypermethylation of microRNA219a-2 in renal fibrosis induced by unilateral ureteral obstruction (UUO) or renal ischemia/reperfusion, which was accompanied by a significant decrease in microRNA-219a-5p expression. Functionally, overexpression of microRNA219a-2 enhanced fibronectin induction during hypoxia or TGF-β1 treatment of cultured renal cells. In mice, inhibition of microRNA-219a-5p suppressed fibronectin accumulation in UUO and ischemic/reperfused kidneys. Aldehyde dehydrogenase 1 family member L2 (ALDH1L2) was identified to be the direct target gene of microRNA-219a-5p in renal fibrotic models. MicroRNA-219a-5p suppressed ALDH1L2 expression in cultured renal cells, while inhibition of microRNA-219a-5p prevented the decrease of ALDH1L2 in injured kidneys. Knockdown of ALDH1L2 enhanced plasminogen activator inhibitor-1 (PAI-1) induction during TGF-β1 treatment of renal cells, which was associated with fibronectin expression. In conclusion, the hypermethylation of microRNA219a-2 in response to fibrotic stress may attenuate microRNA-219a-5p expression and induce the upregulation of its target gene ALDH1L2, which reduces fibronectin deposition by suppressing PAI-1.
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