Metastasis‐associated protein 1 promotes epithelial‐mesenchymal transition in idiopathic pulmonary fibrosis by up‐regulating Snail expression

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive and usually fatal lung disease that lacking effective interventions. It is well known that aberrant activation of transforming growth factor‐beta1 (TGF‐β1) frequently promotes epithelial‐mesenchymal transition (EMT) in IPF. Metastasis‐associated gene 1 (MTA1) has identified as an oncogene in several human tumours, and aberrant MTA1 expression has been related to the EMT regulation. However, its expression and function in IPF remain largely unexplored. Using a combination of in vitro and in vivo studies, we found that MTA1 was significantly up‐regulated in bleomycin‐induced fibrosis rats and TGF‐β1‐treated alveolar type Ⅱ epithelial (RLE‐6TN) cells. Overexpression of MTA1 induced EMT of RLE‐6TN cells, as well as facilitates cell proliferation and migration. In contrast, knockdown of MTA1 reversed TGF‐β1‐induced EMT of RLE‐6TN cells. The pro‐fibrotic action of MTA1 was mediated by increasing Snail expression through up‐regulating Snail promoter activity. Moreover, inhibition of MTA1 effectively attenuated bleomycin‐induced fibrosis in rats. Additionally, we preliminarily found astragaloside IV (ASV), which was previously validated having inhibitory effects on TGF‐β1‐induced EMT, could inhibit MTA1 expression in TGF‐β1‐treated RLE‐6TN cells. These findings highlight the role of MTA1 in TGF‐β1‐mediated EMT that offer novel strategies for the prevention and treatment of IPF.

Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial–mesenchymal transition and inflammation

“…This is in stark contrast to our finding. However, research on EMT in pulmonary fibrosis has been still reported in the lots of literatures recently [61][62][63][64][65][66] . There is no conclusion in this field.…”

Estrogen attenuates TGF-β1-induced EMT in intrauterine adhesion by activating Wnt/β-catenin signaling pathway

“…Increased expression of TGF-β has been reported to be closely related to poor prognosis of multiple diseases ( 22 ). In addition, TGF-β is intimately linked to the initiation of EMT that plays a predominant role in fibrosis disease ( 23 ). However, the function of estrogen on TGF-β-induced EMT in IUA remains unclear.…”

“…First, our results demonstrated that different concentrations of estrogen had different effects on normal endometrial epithelial cells, and relatively high doses of estrogen (30 nM) inhibited cell proliferation by promoting the progress of EMT in normal endometrium. Previous studies found that estrogen was sensitive to EMT progression in endometrial cancer and endometriosis (24,25). Since endometrial fibrosis is the main cause of IUA occurrence and poor prognosis, we further investigated the impact of the same dose of estrogen on EMT in the fibrotic environment.…”

Epithelial–Mesenchymal Transition: A Major Pathogenic Driver in Idiopathic Pulmonary Fibrosis?

“…Important knowledge was added to the field after the publication of our review paper. Notably, Su et al found that RAS-responsive element binding protein 1 (RREB1) is a key partner of TGF-β-activated SMAD transcription factors in EMT [ 9 ], while Qian and coauthors identified the oncogene metastasis-associated protein 1 (MTA1) to be significantly upregulated in TGF-β-mediated EMT both in vitro and in vivo [ 10 ]. Recently, Saito et al demonstrated that the constitutionally activated mammalian target of Rapamycin (mTOR) pathway in the ATII cells of transgenic mice resulted in an exacerbation of bleomycin-induced lung fibrosis and that mTOR-transfected ATIIs showed an enhanced expression of EMT markers after treatment with TGFβ1 [ 11 ].…”