microRNA-1246 mediates lipopolysaccharide-induced pulmonary endothelial cell
apoptosis and acute lung injury by targeting angiotensin-converting enzyme 2
#MMPMID28386354
Fang Y
; Gao F
; Hao J
; Liu Z
Am J Transl Res
2017[]; 9
(3
): 1287-1296
PMID28386354
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In this study, we aimed to identify potential microRNA (miRNA) regulators of
angiotensin-converting enzyme 2 (ACE2) and to explore their roles in
lipopolysaccharide (LPS)-induced acute lung injury (ALI). The expression of
predicted miRNA regulators of ACE2 was examined in LPS-exposed pulmonary
microvascular endothelial cells (PMVECs). Gain- and loss-of-function studies were
performed to determine the functions of candidate miRNAs in LPS-induced PMVEC
apoptosis and inflammatory response. The roles of the miRNAs in LPS-induced lung
inflammation and permeability were investigated in a mouse model. Notably, LPS (1
?g/mL) significantly induced the expression of miR-1246 in PMVECs. ACE2 was
validated as a target gene of miR-1246. Silencing of miR-1246 prevented
LPS-induced inhibition of ACE2, which was accompanied by reduced apoptosis and
production of IL-1? and TNF-?. In contrast, ectopic expression of miR-1246
triggered apoptosis in PMVECs and promoted IL-1? and TNF-? release.
MiR-1246-mediated apoptosis of PMVECs was impaired by overexpression of ACE2.
Depletion of miR-1246 attenuated lung inflammation, neutrophil infiltration, and
vascular permeability and restored pulmonary expression of ACE2 in LPS-exposed
mice. Taken together, miR-1246 meditates LPS-induced pulmonary endothelial cell
apoptosis in vitro and ALI in mouse models, which are, at least partially,
ascribed to repression of ACE2.
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