miR -135a-5p regulates inflammation-induced myocardial fibrosis by targeting APCs

Background: Explore the mechanism of miR-135a-5p on the progression of myocardial fibrosis (MF). Methods: A total of 66 rats were used to construct the MF model. Hematoxylin-eosin(HE) staining was used to reveal the morphological characteristics of myocardial tissues. The expression of fibrosis markers and inflammatory factors were identified by ELISA as well as RT-qPCR, respectively. Bioinformatics was used to screen molecules specifically expressed in MF and its effect on rats MF progression. The effect of miR-135a-5p on the expression of target molecule was identified by dual luciferase reporter assay. The effect of APC on fibrosis markers and inflammatory factors in mice MF model was detected. Ang II-stimulated human fibroblastic cardiomyocytes (HAFs) were constructed as a MF cell model, and miR-135a-5p and APC were detected for their effect on fibrotic progression in Ang II-stimulated HAFs. Results: In the rats MF model, collagen deposition was increased, transverse striations was disappeared, myofibrillar structure was unclear, reticular fibrosis was seen. The Col1a1, α-SMA, Collagen II, and TNF-α, IL-6 were increased. miR-135a-5p was highly expressed in MF and overexpression of miR-135a-5p stimulated the fibrotic process. miR-135a-5p decreased APC luciferase activity and APC expression was low in MF, and stimulation of APC attenuated the fibrotic process. Conclusion: The activation of APC can attenuate the fibrosis-stimulating effect exerted by miR-135a-5p, thereby mitigating the progression of fibrosis and inflammatory response.