The microRNA miR-17 regulates lung FoxA1 expression during lipopolysaccharide-induced acute lung injury.
Acute lung injury (ALI) is a severe pulmonary disease that causes a high number of fatalities worldwide. Studies have shown that FoxA1 expression is upregulated during ALI and may play an important role in ALI by promoting the apoptosis of alveolar type II epithelial cells. However, the mechanism of FoxA1 overexpression in ALI is unclear. In this study, an in vivo murine model of ALI and alveolar type II epithelial cells injury was induced using lipopolysaccharide (LPS). LPS upregulated FoxA1 in the lung tissue of the in vivo ALI model and in LPS-challenged type II epithelial cells. In contrast, miR-17 was significantly downregulated in these models. After miR-17 antagomir injection, the expression of FoxA1 was significantly increased in ALI mice. MiR-17 mimics could significantly inhibit FoxA1 mRNA and protein expression, whereas the miR-17 inhibitor could significantly increase FoxA1 mRNA and protein expression in LPS-induced type II epithelial cells. Thus, our results suggest that the downregulation of miR-17 expression could lead to FoxA1 overexpression in ALI.
Cardiothoracic Surgery of the First Affiliated Hospital, Hunan University of Traditional Chinese Medicine, Changsha, Hunan 41007, China.
Zhaojun
Z
Xu
University of South China, College of Life Science, Department of Biochemistry and Molecular Biology, Hengyang, Hunan 421001, China.
Caiping
C
Zhang
Department of Biochemistry and Molecular Biology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.
Lijuan
L
Cheng
Department of Biochemistry and Molecular Biology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.
Mei
M
Hu
Department of Biochemistry and Molecular Biology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.
Huai
H
Tao
Department of Biochemistry and Molecular Biology, Hunan University of Chinese Medicine, 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, Changsha, Hunan 410208, China; University of South China, College of Life Science, Department of Biochemistry and Molecular Biology, Hengyang, Hunan 421001, China. Electronic address: songlan311492@163.com.
Lan
L
Song
D055371:Acute Lung Injury / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D055785:Gene Knockdown Techniques; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
C496500:Foxa1 protein, mouse; D051541:Hepatocyte Nuclear Factor 3-alpha; D008070:Lipopolysaccharides; D035683:MicroRNAs; C543614:Mirn17 microRNA, mouse
Acute lung injury; Alveolar type II epithelial cells; FoxA1; Gene expression; miR-17