miR-29b-1-5p exacerbates myocardial injury induced by sepsis in a mouse model by targeting TERF2

In this study, we explore the effect and mechanisms of miR-29b-1-5p on sepsis-induced myocardial damage. Sepsis-associated Gene Expression Omnibus (GEO) datasets (GSE72380 and GSE29914) are examined for differential miRNAs. The mouse sepsis-induced cardiac injury was established by Lipopolysaccharide (LPS) or cecal ligation and puncture (CLP). LPS-treated HL-1 mouse cardiomyocytes simulate myocardial injury in vitro. miR-29b-1-5p is co-upregulated in both datasets and in cardiac tissue from sepsis mouse and HL-1 cell models. miR-29b-1-5p expression downregulation was achieved by antagomir transduction and confirmed by real-time quantitative reverse transcription PCR (qRT-PCR). Survival analysis and echocardiography examination show that miR-29b-1-5p inhibition improves mice survival cardiac function in LPS- and CLP-induced sepsis mice. Hematoxylin and Eosin (H&E) and Masson's trichrome staining and Immunohistochemistry (IHC) analysis of mouse myocardial α-smooth muscle actin (α-SMA) show that miR-29b-1-5p inhibition reduces myocardial tissue injury and fibrosis. The inflammatory cytokines and cardiac troponin I (cTnI) levels in mouse serum and HL-1 cells are also decreased by miR-29b-1-5p inhibition, as revealed by enzyme-linked immunosorbent assay (ELISA). The expressions of autophagy-lysosomal pathway-related and apoptosis-related proteins in the mouse cardiac tissues and HL-1 cells are evaluated by western blot analysis. The sepsis-induced activation of the autophagy...
Source: Acta Biochimica et Biophysica Sinica - Category: Biochemistry Authors: Source Type: research