High expression of miR-483-5p aggravates sepsis-induced acute lung injury.

ABSTRACT

Sepsis-induced acute lung injury (ALI) has high morbidity and mortality rates, and there remains a need for therapeutic methods to improve the outcome of ALI patients. miR-483-5p is an important regulator for the development of various diseases such as sepsis. Nevertheless, it is not known whether miR-483-5p has an effect on sepsis-induced ALI. To explore this issue, this study used cecal ligation and puncture (CLP)-treated mice and lipopolysaccharide (LPS)-treated pulmonary microvascular endothelial cells (PMVECs) cells to simulate the models of sepsis-induced ALI in vivo and in vitro. Pathological and histological changes of lungs from sepsis-induced ALI mice were detected by Hematoxylin-eosin staining. The detection levels of caspase-3, interleukin (IL)-6 and IL-1ß were used to reflect the effect of miR-483-5p on apoptosis and inflammation of sepsis-induced ALI. The detection level of lactate dehydrogenase (LDH) in PMVECs cells was used to reflect the severe extent of sepsis-induced injury. The expression of miR-483-5p in lung tissues of sepsis-induced ALI mice was determined by qRT-PCR. In addition, the interaction of miR-483-5p with PIAS1 was identified and validated by Targetscan website and luciferase reporter assay, respectively. The results showed that miR-483-5p was up-regulated in the lung tissues of sepsis-induced ALI mice. Knockdown of miR-483-5p effectively ameliorated lung injury in mice with sepsis-induced ALI and inhibited inflammation and apoptosis of LPS-treated PMVECs cells. Furthermore, in vitro experiment revealed that PIAS1 was a potential target of miR-483-5p. Moreover, miR-483-5p could suppress PIAS1 expression to aggravate inflammation and apoptosis of LPS-treated PMVECs cells. These findings suggest miR-483-5p is a potential therapeutic and diagnostic biomarker for sepsis-induced ALI and provide a new insight for understanding the molecular mechanism of sepsis-induced ALI.