Abstract
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-α (TNF-α) and interleukin (IL)-1β 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.