Dataset Information

MiR-184 targets TP63 to block idiopathic pulmonary fibrosis by inhibiting proliferation and epithelial-mesenchymal transition of airway epithelial cells.

ABSTRACT: Epithelial-to-mesenchymal transition (EMT) of epithelium and airway epithelial cell proliferation disorder are key events in idiopathic pulmonary fibrosis (IPF) pathogenesis. During EMT, epithelial cell adhesion molecules (EpCAM, such as E-cadherin) are downregulated, cytokeratin cytoskeletal transforms into vimentin-based cytoskeleton, and the epithelial cells acquire mesenchymal morphology. In the present study, we show abnormal upregulation of tumor protein p63 (TP63) and downregulation of miR-184 in IPF. Transforming growth factor beta 1 (TGF-?1) stimulation of BEAS-2B and A549 cell lines significantly increased the protein levels of Tp63, alpha-smooth muscle actin (?-SMA), and vimentin, but decreased EpCAM protein levels, and promoted viability of both BEAS-2B and A549 cell lines. TP63 knockdown in BEAS-2B and A549 cell lines significantly attenuated above-described TGF-?1-induced fibrotic changes. miR-184 targeted TP63 3'-UTR to inhibit Tp63 expression. miR-184 overexpression within BEAS-2B and A549 cell lines also attenuated TGF-?1-induced fibrotic changes. miR-184 overexpression attenuated bleomycin-induced pulmonary fibrosis in mice. Moreover, TP63 overexpression aggravated TGF-?1-stimulated fibrotic alterations within BEAS-2B and A549 cells and significantly reversed the effects of miR-184 overexpression, indicating miR-184 relieves TGF-?1-stimulated fibrotic alterations within BEAS-2B and A549 cells by targeting TP63, while TP63 overexpression reversed miR-184 cellular functions. In conclusion, the miR-184/TP63 axis modulates the TGF-?1-induced fibrotic alterations in epithelial cell lines and bleomycin-induced pulmonary fibrosis in mice. Therefore, these results confirm that the miR-184/TP63 axis is involved in IPF progression.

SUBMITTER: Li J

PROVIDER: S-EPMC7815506 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

miR-184 targets TP63 to block idiopathic pulmonary fibrosis by inhibiting proliferation and epithelial-mesenchymal transition of airway epithelial cells.

Li Jianmin J Pan Chanyuan C Tang Chao C Tan Wenwen W Zhang Weiwei W Guan Jing J

Laboratory investigation; a journal of technical methods and pathology 20200928 2

Epithelial-to-mesenchymal transition (EMT) of epithelium and airway epithelial cell proliferation disorder are key events in idiopathic pulmonary fibrosis (IPF) pathogenesis. During EMT, epithelial cell adhesion molecules (EpCAM, such as E-cadherin) are downregulated, cytokeratin cytoskeletal transforms into vimentin-based cytoskeleton, and the epithelial cells acquire mesenchymal morphology. In the present study, we show abnormal upregulation of tumor protein p63 (TP63) and downregulation of mi ...[more]

PMID: 32989231

Similar Datasets

Project description:BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease with no effective treatment. The epithelial-mesenchymal transition (EMT) is a critical stage during the development of fibrosis. To assess the effect of sulforaphane (SFN) on the EMT and fibrosis using an in vitro transforming growth factor (TGF)-β1-induced model and an in vivo bleomycin (BLM)-induced model.MethodsIn vitro studies, cell viability, and cytotoxicity were measured using a Cell Counting Kit-8. The functional TGF-β1-induced EMT and fibrosis were assessed using western blotting and a quantitative real-time polymerase chain reaction. The lungs were analyzed histopathologically in vivo using hematoxylin and eosin and Masson's trichrome staining. The BLM-induced fibrosis was characterized by western blotting and immunohistochemical analyses for fibronectin, TGF-β1, E-cadherin (E-cad), and α-smooth muscle actin (SMA) in lung tissues.ResultsSFN reversed mesenchymal-like changes induced by TGF-β1 and restored cells to their epithelial-like morphology. The results confirmed that the expression of the epithelial marker, E-cadherin, increased after SFN treatment, while expression of the mesenchymal markers, N-cadherin, vimentin, and α-SMA decreased in A549 cells after SFN treatment. In addition, SFN inhibited TGF-β1-induced mRNA expression of the EMT-related transcription factors, Slug, Snail, and Twist. The SFN treatment attenuated TGF-β1-induced expression of fibrosis-related proteins, such as fibronection, collagen I, collagen IV, and α-SMA in MRC-5 cells. Furthermore, SFN reduced the TGF-β1-induced phosphorylation of SMAD2/3 protein in A549 cells and MRC-5 cells. BLM induced fibrosis in mouse lungs that was also attenuated by SFN treatment, and SFN treatment decreased BLM-induced fibronectin expression, TGF-β1 expression, and the levels of collagen I in the lungs of mice.ConclusionsSFN showed a significant anti-fibrotic effect in TGF-β-treated cell lines and BLM-induced fibrosis in mice. These findings showed that SFN has anti-fibrotic activity that may be considered in the treatment of IPF.

Dataset Information

MiR-184 targets TP63 to block idiopathic pulmonary fibrosis by inhibiting proliferation and epithelial-mesenchymal transition of airway epithelial cells.

Publications

miR-184 targets TP63 to block idiopathic pulmonary fibrosis by inhibiting proliferation and epithelial-mesenchymal transition of airway epithelial cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets