MicroRNA-21 protects against sepsis-induced acute lung injury by targeting phosphatase and tensin homolog in mice

Abstract

Introduction: Sepsis can cause acute lung injury (ALI), one of the leading causes of death in critically ill patients. The underlying mechanisms of sepsis-induced acute lung injury include excessive inflammation, oxidative stress, cell apoptosis, pulmonary edema, and lung tissue dysfunction. Recent studies have shown that miRNA-21 (miR-21) plays a vital role in sepsis-induced acute kidney injury. Relatively few studies have focused on the protective effects of ALI. This study aimed to determine the potential role of miR-21 in sepsis-induced ALI. Methods: We performed quantitative real-time polymerase chain reaction in a septic mouse model induced by cecal ligation and puncture (CLP) and found that miR-21 expression was upregulated. We then transfected the miR-21 precursor to upregulate miR-21 expression and miR-21 inhibitor to downregulate miR-21 expression. The sham group was exposed only to the cecum. ALI was induced by CLP, and the pre-miR-21+ALI and anti-miR-21+ALI groups were treated with miR-21 precursor or miR-21 inhibitor in the caudal vein before CLP. Pre-miR-21+ALI+PTEN inhibition (Pre-miR-21+ALI+PI) and anti-miR-21+ALI+PTEN inhibition (Anti-miR-21+ALI+PI) groups were treated with PTEN inhibition into the caudal vein after miR-21 transfection. Inflammatory cytokines, oxidative stress indicators, lung tissue cell apoptosis, oxygenation index (OI), lung wet/dry weight ratio, and lung pathological changes in the lung were observed in each group. Results: Compared with ALI mice, inflammatory response, oxidative stress indicators, lung tissue cell apoptosis, and the degree of lung injury were remarkably alleviated in Pre-miR-21+ALI mice and aggravated in Anti-miR-21+ALI mice. Western blot analysis showed that phosphatase and tensin homolog (PTEN) protein expression was decreased in CLP-treated mics. PTEN protein expression was decreased in the Pre-miR-21+ALI group but increased in the Anti-miR-21+ALI group. Moreover, the effect of miR-21 on anti-inflammatory, anti-oxidative stress, and anti-apoptosis enhanced after PTEN inhibition. Conclusion: This study revealed that miR-21 has a protective effect in sepsis-induced ALI by regulating PTEN in mice.