miR-205 Suppresses Pulmonary Fibrosis by Targeting GATA3 Through Inhibition of Endoplasmic Reticulum Stress
Autor: | Bingke Sun, Jianwen Bai, Tiancao Dong, Yanli Yan, Shumin Xu, Hongqiang Li, Yusheng Li, Guizhen Zheng |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Pulmonary Fibrosis Pharmaceutical Science Down-Regulation GATA3 Transcription Factor Lung injury CHOP Bleomycin Collagen Type I Cell Line Rats Sprague-Dawley Transforming Growth Factor beta1 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Fibrosis In vivo Pulmonary fibrosis medicine Animals Reporter gene medicine.disease Endoplasmic Reticulum Stress Actins Rats Up-Regulation Blot Disease Models Animal MicroRNAs 030104 developmental biology chemistry 030220 oncology & carcinogenesis Cancer research Biotechnology Protein Binding |
Zdroj: | Current pharmaceutical biotechnology. 21(8) |
ISSN: | 1873-4316 |
Popis: | Objective: To investigate the role of miR-205 and GATA3 in Pulmonary Fibrosis (PF). Methods: Bleomycin (BLM) was used to induce PF in SD rats and in vitro PF model was established by using TGFβ1-induced RLE-6TN cells. miR-205 mimics were used for the overexpression of miR- 205. The expression of miR-205, GATA3, α-SMA, Collagen I, CHOP and GRP78 were measured using RT-qPCR or western blotting. Dual-luciferase reporter assay was used to confirm binding between GATA3 3’-UTR and miR-205. Results: The expression of miR-205 was significantly down-regulated, while the expression of GATA3 was remarkably up-regulated in the model rats. GATA3 levels were remarkably decreased when miR-205 was overexpressed. When miR-205 was overexpressed, the lung injury by BLM-induced fibrosis was improved. The expression of α-SMA, Collagen I, as well as GRP78 and CHOP, was significantly up-regulated in both in vivo and in vitro PF models, and overexpression of miR-205 remarkably reversed the effects. Dual-luciferase reporter assay showed that miR-205 directly targeted and negatively regulated GATA3. Conclusion: miR-205 improved pulmonary fibrosis through inhibiting ER-stress by targeting GATA3. |
Databáze: | OpenAIRE |
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