Abstract
The protective effect of microRNA (miR)-145-5p in acute lung injury (ALI) has been discovered previously. Thus, in this study, we attempted to further investigate the mechanism of miR-145-5p in ALI through the downstream E26 transformation-specific proto-oncogene 2 (ETS2)/transforming growth factor β1 (TGF-β1)/Smad pathway. A lipopolysaccharide (LPS)-induced ALI rat model was established. The expression of miR-145-5p in ALI rat lung tissues was up-regulated. Afterward, pathological damage in the lung tissue, the wet/dry (W/D) ratio, apoptosis, and serum inflammatory factor contents were observed. miR-145-5p, ETS2, TGF-β1, Smad2/3, and phosphorylated Smad2/3 levels were measured in rats. miR-145-5p expression was down-regulated, ETS2 expression was up-regulated, and the TGF-β1/Smad pathway was activated in LPS-exposed rats. Overexpression of miR-145-5p inactivated the TGF-β1/Smad pathway and attenuated ALI, as reflected by relieved pathological damage, a decreased W/D ratio, reduced apoptosis, and suppressed inflammatory response. In contrast, loss of miR-145-5p or elevated ETS2 levels worsened ALI and activated the TGF-β1/Smad pathway. Moreover, elevation of ETS2 diminished miR-145-5p-mediated protection against ALI. Evidently, miR-145-5p negatively regulates ETS2 expression and inactivates the TGF-β1/Smad pathway to ameliorate ALI in rats.