YY1 mediates TGF-?1-induced EMT and pro-fibrogenesis in alveolar epithelial cells.
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ABSTRACT: Pulmonary fibrosis is a chronic, progressive lung disease associated with lung damage and scarring. The pathological mechanism causing pulmonary fibrosis remains unknown. Emerging evidence suggests prominent roles of epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AECs) in myofibroblast formation and progressive pulmonary fibrosis. Our previous work has demonstrated the regulation of YY1 in idiopathic pulmonary fibrosis and pathogenesis of fibroid lung. However, the specific function of YY1 in AECs during the pathogenesis of pulmonary fibrosis is yet to be determined. Herein, we found the higher level of YY1 in primary fibroblasts than that in primary epithelial cells from the lung of mouse. A549 and BEAS-2B cells, serving as models for type II alveolar pulmonary epithelium in vitro, were used to determine the function of YY1 during EMT of AECs. TGF-?-induced activation of the pro-fibrotic program was applied to determine the role YY1 may play in pro-fibrogenesis of type II alveolar epithelial cells. Upregulation of YY1 was associated with EMT and pro-fibrotic phenotype induced by TGF-? treatment. Targeted knockdown of YY1 abrogated the EMT induction by TGF-? treatment. Enforced expression of YY1 can partly mimic the TGF-?-induced pro-fibrotic change in either A549 cell line or primary alveolar epithelial cells, indicating the induction of YY1 expression may mediate the TGF-?-induced EMT and pro-fibrosis. In addition, the translocation of NF-?B p65 from the cytoplasm to the nucleus was demonstrated in A549 cells after TGF-? treatment and/or YY1 overexpression, suggesting that NF-?B-YY1 signaling pathway regulates pulmonary fibrotic progression in lung epithelial cells. These findings will shed light on the better understanding of mechanisms regulating pro-fibrogenesis in AECs and pathogenesis of lung fibrosis.
SUBMITTER: Zhang C
PROVIDER: S-EPMC6839144 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
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