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 II-stimulated 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.

To Cite This Article: Xia Y, Zeng L, Ding T, Zhang B, Li D and Cui D, 2025. miR-135a-5p regulates inflammation-induced myocardial fibrosis by targeting APCs (Adenomatous Polyposis Coli). Pak Vet J. http://dx.doi.org/10.29261/pakvetj/2025.129