miR-135a-5p Regulates Inflammation-Induced Myocardial Fibrosis by Targeting APCs (Adenomatous Polyposis Coli)
Year: 2025
Type: article
Abstract: Myocardial fibrosis is a critical pathological process contributing to heart failure, characterized by excessive extracellular matrix (ECM) deposition and inflammation.This study investigates the role of miR-135a-5p and its target gene APC in MF pathogenesis.Bioinformatics analysis using TargetScan and the Human miRNA Tissue Atlas revealed tissue-specific expression of miR-135a-5p, with significant levels in the myocardium, thyroid, and epididymis.An in vivo rat MF model was established using cardiac ischemia/reperfusion injury, confirmed by histopathological changes, including collagen deposition and loss of myocyte nuclei.miR-135a-5p was upregulated in MF tissues, and its modulation significantly influenced fibrosis and inflammation.miR-135a-5p mimics increased fibrosis markers (α-SMA, Col1a1, Collagen II) and pro-inflammatory cytokines (TNF-α, IL-6), while miR-135a-5p inhibition attenuated these effects.TargetScan and dual luciferase assays identified APC as a direct target of miR-135a-5p, with miR-135a-5p binding to the 3'UTR of APC mRNA.The effect of APC on fibrosis markers and inflammatory factors in the rat MF model was detected.Co-activation of miR-135a-5p and APC in the rat MF model attenuated fibrosis and inflammation, highlighting the regulatory role of the miR-135a-5p/APC axis.In vitro, Ang IIstimulated human atrial fibroblasts (HAFs) exhibited elevated miR-135a-5p, reduced APC, and increased fibrosis markers and proliferation.miR-135a-5p activation promoted fibrosis and inflammation, while activation of APC attenuates miR-135a-5p-induced fibrosis and inflammation in myocardial tissues.These findings highlight the miR-135a-5p/APC axis as a potential therapeutic target for MF.
Source: Pakistan Veterinary Journal
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $300
OpenAlex ID: W4408842792