Up-regulation of microRNA-574 attenuates lipopolysaccharide- or cecal ligation and puncture-induced sepsis associated with acute lung injury

Acute lung injury (ALI) is the most vulnerable organ in sepsis, however, its underlying mechanism remains unclear. Cell viability and apoptosis were detected by cell counting kit-8 and flow cytometry. The expressions of miR-574, Complement 3 (C3), glucose regulatory protein 78 (GRP78), C/EBP homologous protein (CHOP) and Caspase-12 were determined using quantitative real time (qRT)-PCR and Western blot. Histopathology of mice was stained by haematoxylin and eosin staining. The levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 beta were determined using ELISA. The expression of miR-574 was positively correlated with cell viability in lipopolysaccharide (LPS)-treated cells. Cell viability was improved and apoptosis was inhibited by mimics. Meanwhile, the levels of GRP78, CHOP and Caspase-12 were suppressed by mimics and agomir in LPS-treated human bronchial epithelial (HBE) cells and cecal ligation and puncture (CLP)-treated mice. In vivo, lung tissue damages were ameliorated by agomir, which also decreased the levels of neutrophils, macrophages and albumin. C3 was a target gene of miR-574 and could be decreased by mimics. SiC3 enhanced cell viability and inhibited apoptosis, however, it suppressed the mRNA levels of GRP78, CHOP and Caspase-12. Up-regulation of miR-574 attenuated sepsis-induced lung injury may be by promoting C3 down-regulation and reducing sepsis-induced endoplasmic reticulum stress (ERS). Significance of the study Clinically, the mortality rate of ALI induced by sepsis remains at a high level, thus, clarifying the mechanism of induction of ALI through pathogen infection will provide a new target for clinical treatment of ALI. In this study, up-regulation of miR-574 attenuated sepsis-induced lung injury may be by promoting C3 down-regulation and reducing sepsis-induced ERS. Our study provides a deeper understanding of sepsis.