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miR-205 Suppresses Pulmonary Fibrosis by Targeting GATA3 Through Inhibition of Endoplasmic Reticulum Stress

[ Vol. 21 , Issue. 8 ]

Author(s):

Bingke Sun, Shumin Xu, Yanli Yan, Yusheng Li, Hongqiang Li, Guizhen Zheng, Tiancao Dong and Jianwen Bai*   Pages 720 - 726 ( 7 )

Abstract:


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.

Keywords:

miR-205, pulmonary fibrosis, GATA3, CHOP, endoplasmic reticulum stress, alveolar epithelial cells.

Affiliation:

Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tong Ji University, Shanghai 200120, Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tong Ji University, Shanghai 200120, Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tong Ji University, Shanghai 200120, Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tong Ji University, Shanghai 200120, Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tong Ji University, Shanghai 200120, Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tong Ji University, Shanghai 200120, Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tong Ji University, Shanghai 200120, Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tong Ji University, Shanghai 200120



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