MicroRNA-34a Suppresses Autophagy in Alveolar Type II Epithelial Cells in Acute Lung Injury by Inhibiting FoxO3 Expression.
Excessive autophagic activity of alveolar type II epithelial (AT-II) cells is one of the main causes of acute lung injury (ALI); however, the underlying molecular mechanism remains to be determined. The microRNAs (miRNAs) are involved with autophagy in many diseases. The objective of this study was therefore to investigate the relationship between the miRNA expression and the autophagic activity of the AT-II cells in the pathogenesis of ALI and its molecular mechanism. A mouse model of ALI and AT-II cell injury was induced using lipopolysaccharide (LPS) in vivo and in vitro, and the expression of miR-34a and the autophagy-related proteins LC3 II/I and p62 were determined. Moreover, the autophagic activity was investigated after miR-34a overexpression and inhibition. The effects of miR-34a on its target gene, FoxO3, in regulating autophagic activity in AT-II cells were also determined. LPS induced autophagic activity and increased the expression of miR-34a in lung tissues and in AT-II cells. The in vitro results showed that the upregulation of miR-34a suppressed, whereas the inhibition of miR-34a promoted, autophagy in AT-II cells. Moreover, miR-34a could directly bind to the 3'-untranslated region of the autophagy-related gene, FoxO3, to decrease its expression. In addition, the knockdown of FoxO3 expression inhibited the autophagic activity in AT-II cells. Together, this study suggested that miR-34a might suppress the excessive autophagic activity in AT-II cells via targeting FoxO3 to reduce the damage of LPS-induced ALI.
Department of Biochemistry and Molecular Biology, Hunan University of Chinese Medicine, 300 Xueshi Road, Hanpu Science and Teaching Park, Changsha, Hunan, 410208, China.|Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (Incubation), Hunan University of Chinese Medicine, 300 Xueshi Road, Hanpu Science and Teaching Park, Changsha, Hunan, 410208, China.
Lan
L
Song
Department of Biochemistry and Molecular Biology, Hunan University of Chinese Medicine, 300 Xueshi Road, Hanpu Science and Teaching Park, Changsha, Hunan, 410208, China.|Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (Incubation), Hunan University of Chinese Medicine, 300 Xueshi Road, Hanpu Science and Teaching Park, Changsha, Hunan, 410208, China.
Fangliang
F
Zhou
Department of Biochemistry and Molecular Biology, Hunan University of Chinese Medicine, 300 Xueshi Road, Hanpu Science and Teaching Park, Changsha, Hunan, 410208, China.
Lijuan
L
Cheng
Department of Biochemistry and Molecular Biology, Hunan University of Chinese Medicine, 300 Xueshi Road, Hanpu Science and Teaching Park, Changsha, Hunan, 410208, China.
Mei
M
Hu
Department of Biochemistry and Molecular Biology, Hunan University of Chinese Medicine, 300 Xueshi Road, Hanpu Science and Teaching Park, Changsha, Hunan, 410208, China.
Yingchun
Y
He
Department of Biochemistry and Molecular Biology, Hunan University of Chinese Medicine, 300 Xueshi Road, Hanpu Science and Teaching Park, Changsha, Hunan, 410208, China.
Bo
B
Zhang
Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (Incubation), Hunan University of Chinese Medicine, 300 Xueshi Road, Hanpu Science and Teaching Park, Changsha, Hunan, 410208, China. dfliao66@aliyun.com.
Duanfang
D
Liao
Cardiothoracic Surgery of the First Affiliated Hospital, Hunan University of Chinese Medicine, 97 Shaoshan Road, Changsha, Hunan, 41007, China. Xuzj1492@163.com.
Zhaojun
Z
Xu
D055371:Acute Lung Injury / Q000139:chemically induced / Q000209:etiology / Q000473:pathology*; D056809:Alveolar Epithelial Cells / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000235:genetics*; D000071316:Forkhead Box Protein O3 / Q000037:antagonists & inhibitors*; D008070:Lipopolysaccharides; D051379:Mice; D035683:MicroRNAs / Q000494:pharmacology / Q000502:physiology*; D008869:Microtubule-Associated Proteins
D000071316:Forkhead Box Protein O3; C474033:FoxO3 protein, mouse; D008070:Lipopolysaccharides; C551848:MIRN34a microRNA, mouse; C480860:Map1lc3b protein, mouse; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins
FoxO3; acute lung injury; alveolar type II epithelial cells; autophagy; miR-34a