MicroRNA-214-3p Ameliorates LPS-Induced Cardiomyocyte Injury by Inhibiting Cathepsin B

Abstract

Myocardial injury is a common complication of sepsis. MicroRNA (miRNA) miR-214-3p is protective against myocardial injury caused by sepsis, but its mechanism in lipopolysaccharide (LPS)- induced cardiomyocyte injury is still unclear. An AC16 cell injury model was induced by LPS treatment. Cell Counting Kit-8 and flow cytometry assay showed decreased cell viability and increased apoptosis in LPS-treated AC16 cells. The levels of caspase- 3, Bax, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), myosin 6 (Myh6), myosin 7 (Myh7), reactive oxygen species (ROS), and malondialdehyde (MDA) were increased in LPS-treated AC16 cells, but the levels of Bcl-2 and superoxide dismutase (SOD) were decreased. MiR-214-3p was down-regulated and cathepsin B (CTSB) was upregulated in LPS-treated AC16 cells. At the same time, miR-214-3p could target CTSB and reduce its expression. We also found that a miR-214-3p mimic or CTSB silencing could significantly reduce LPSinduced apoptosis, decrease ROS, MDA, caspase-3, and Bax and increase SOD and Bcl-2. CTSB silencing could significantly reduce ANP, BNP, Myh6, and Myh7 in LPS-treated AC16 cells. The effects of CTSB silencing were reversed by a miR-214-3p inhibitor. In summary, miR-214-3p could inhibit LPSinduced myocardial injury by targeting CTSB, which provides a new idea for myocardial damage caused by sepsis.

Research Progress of Macromolecules in the Prevention and Treatment of Sepsis

“…Moreover, it can reduce LPS-induced inflammation, oxidative stress, and apoptosis, and improve LPS-induced brain injury in septic rats [ 67 ]. miR-214-3p can inhibit the expression of cathepsin B, regulate the levels of anti-apoptotic bcl-2 and pro-apoptotic proteins Bax and caspase-3, decrease the levels of ROS and MDA, increase the proportion of SOD, reduce the apoptosis and oxidative damage of AC16 cells stimulated by LPS, and improve myocardial injury caused by sepsis [ 68 ]. miR-340-5p can reduce the expression of myeloid differentiation factor 88 protein, inhibit the elevated production of ROS and MDA induced by LPS, increase the level of GSH, reduce the oxidative stress response of sepsis-induced cardiomyopathy (SIC) cell model, and improve LPS-induced HL-1 cell injury.…”