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.

目的：探讨miR-205和GATA3在肺纤维化（PF）中的作用。

方法：用博来霉素（BLM）诱导SD大鼠的PF，并用TGFβ1诱导的RLE-6TN细胞建立体外PF模型。miR-205模拟物用于miR-205的过表达。miR-205，GATA3，α-SMA，胶原I，CHOP和GRP78的表达通过RT-qPCR或Western blot检测。使用双重萤光素酶报告基因测定法确认GATA3 3'-UTR与miR-205之间的结合。

结果：在模型大鼠中，miR-205的表达显着下调，而GATA3的表达显着上调。当miR-205过表达时，GATA3水平显着下降。当miR-205过表达时，BLM诱导的纤维化对肺部的损伤得到改善。在体内和体外PF模型中，α-SMA，胶原蛋白I以及GRP78和CHOP的表达均显着上调，miR-205的过表达显着逆转了这种作用。双重荧光素酶报告基因检测表明，miR-205直接靶向并负调控GATA3。

结论：miR-205通过靶向GATA3抑制ER应激改善了肺纤维化。