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.