miR-21 regulates LPS-induced apoptosis and inflammatory injury in rat cardiomyocytes by targeting PLD1 and STAT3.

Abstract

This study aims to elucidate the role and molecular mechanism of microRNA-21 (miR-21) in LPS-induced inflammatory injury in H9c2 cardiomyocytes. H9c2 cardiomyocytes were treated with lipopolysaccharide (LPS) to establish an in vitro model. The expression of miR-21 was quantified using RT-qPCR, while protein levels were assessed via Western blot analysis. The impact of miR-21 on inflamma-tory response, cell proliferation, and apoptosis in LPS-treated H9c2 cells was evalu-ated using ELISA, CCK-8/EdU assays, and flow cytometry. TargetScan predictions and dual-luciferase reporter assays were employed to identify potential miR-21 tar-gets. The regulatory effects of miR-21 on inflammation, proliferation, and apop-tosis in cells were further examined following transfection with phospholipase D1 (PLD1) overexpression constructs or signal transducer and activator of transcription 3 (STAT3) activation. The expression levels of miR-21, PLD1, and p-STAT3 were significantly elevated in LPS-treated H9c2 cells. Knockdown of miR-21 markedly inhibited the LPS-induced inflammatory response, enhanced cell proliferation, and reduced apoptosis in H9c2 cells. PLD1 and STAT3 were confirmed as direct targets of miR-21. Overexpression of PLD1 or activation of STAT3 significantly reversed the protective effects of miR-21 downregulation in LPS-treated H9c2 cells. Downregu-lation of miR-21 protects cardiomyocytes against LPS-induced inflammatory injury and apoptosis by inhibiting PLD1 expression and STAT3 phosphorylation.