The Role of miR-497/EIF3A Axis in TGFβ1-Induced Epithelial-Mesenchymal Transition and Extracellular Matrix in Rat Alveolar Epithelial Cells and Pulmonary Fibroblasts.
Multi-cause-induced interstitial lung disease, particularly pulmonary fibrosis, is a serious clinical concern. Fibroblasts have been suggested to have a major role, with it recently being revealed that some of these fibroblasts are derived from alveolar epithelial cells through epithelial-mesenchymal transition (EMT). Eukaryotic translation initiation factor 3 subunit A (EIF3A) is a protein that in humans is encoded by the EIF3A gene, and has been suggested to play roles in regulating translation of a subset of mRNAs and in regulating cell cycle progression and cell proliferation. In the present study, we chose a well-known TGFβ1-induced EMT model in alveolar epithelial cells to investigate the functional role of EIF3A. TGFβ1-induced EIF3A expression and EMT process in alveolar epithelial cells, after EIF3A knockdown, the EMT process could be partially reversed. Online tools and luciferase assays showed that miR-497 could inhibit EIF3A expression by directly binding to the 3'UTR of EIF3A. Ectopic miR-497 expression partially reversed TGFβ1-induced EMT in alveolar epithelial cells. In addition, miR-497 could suppress TGFβ1-induced pulmonary fibroblast proliferation and EIF3A, Collagen I and α-SMA protein levels. Taken together, EIF3A could promote TGFβ1-induced EMT in alveolar epithelial cells; miR-497 suppressed TGFβ1-induced EMT in alveolar epithelial cells TGFβ1-induced excessive proliferation and ECM in pulmonary fibroblast through inhibiting EIF3A by targeting. MiR-497/EIF3A axis shows the potential to be effective in the treatment of pulmonary fibrosis. J. Cell. Biochem. 118: 3401-3408, 2017. © 2017 Wiley Periodicals, Inc.
National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, 410008, China.|Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410006, China.
Ren
R
Guo
Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410006, China.
Yu
Y
Lv
National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, 410008, China.
Yang
Y
Ouyang
National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, 410008, China.
Siyu
S
Liu
National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, 410008, China.
Dai
0000-0002-1720-5542
D
Li
D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
D039621:Eukaryotic Initiation Factor-3; C000609693:MIRN497 microRNA, rat; D035683:MicroRNAs; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1
ALVEOLAR EPITHELIAL CELL; EIF3A; EPITHELIAL-MESENCHYMAL TRANSITION; PULMONARY FIBROSIS; TGFβ1; miR-497