MicroRNA‑200c‑3p regulates seawater‑induced acute lung injury via ANGII and ACE2/ANG1‑7 pathways.

Abstract

Apoptosis is a main characteristic of seawater aspiration-induced acute lung injury (ALI). The local angiotensin (ANG) system angiotensin converting enzyme (ACE)-2/ANG1-7/Mas axis and ANGII/angiotensin II receptor type 1 (AT1) play an important role in apoptosis. MicroRNA (miR)-200c-3p is involved in the regulation of the ACE-2 pathway, but its role and mechanism in seawater-induced ALI remain to be elucidated. In the present study, seawater-ALI lung tissue and cell model was established and apoptosis-related proteins, ACE2, ANGII, ANG1-7 were detected by western blotting following downregulation of miR-200c-3p. In addition, miR-200c-3p was detected by reverse transcription-quantitative PCR. The target relationship between miR-200c-3p and ACE2 was confirmed by dual-luciferase reporter assay. Seawater stimulation increased the expression of miR-200c-3p, ANGII and decreased ACE-2/ANG1-7 expression and induced changes of apoptosis-related protein expression. Apoptosis can be inhibited by AT1 blocker and abrogated by addition of ANG1-7 following seawater stimulation. In addition, inhibition of miR-200c-3p suppressed apoptosis and decreased the expression of ANGII, but increased the ACE-2/ANG1-7 expression. These results suggested that increased expression of miR-200c-3p was an important cause in seawater-induced ALI and this phenomenon was through inhibition of ACE2/ANG1-7 pathway.