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miR‐627/HMGB1/NF‐κB regulatory loop modulates TGF‐β1‐induced pulmonary fibrosis

Jie Li,Xinyi Kong,Shan Jiang,Wenjian Liao,Zhihui Zhang,Junshuai Song,Ying Liang,Wei Zhang

Published 2018 in Journal of Cellular Biochemistry

ABSTRACT

Pulmonary fibrosis (PF) is a fibroproliferative disease that can eventually lead to fatal lung failure. It is characterized by abnormal proliferation of fibroblasts, dysregulated fibroblast differentiation to myofibroblast, and disorganized collagen and extracellular matrix production, deposition and degradation. There is still a lack of effective treatment strategies for PF. Extracellular high‐mobility group box protein 1 (HMGB1) induces PF through NF‐κB‐mediated TGF‐β1 release. Herein, we first validate the suppressive effect of HMGB1 knockdown on TGF‐β1‐induced α‐smooth muscle actin (α‐SMA) and collagen I protein expression. In PF, miRNAs exert different effects through targeting various downstream target messenger RNAs. We searched an online database for dysregulated miRNAs in PF tissues; among them, miR‐627 was predicted by online tools to target HMGB1 to inhibit its expression. miR‐627 overexpression could partially reverse TGF‐β1‐induced normal human lung fibroblast proliferation, as well as α‐SMA and collagen I protein expression. miR‐627 inhibition could partially reverse the suppressive effect of HMGB1 knockdown on TGF‐β1‐induced α‐SMA and collagen I protein expression through direct binding to the 3′‐untranslated region of HMGB1. Moreover, miR‐627/HMGB1 affected TGF‐β1 release through RAGE/NF‐κB signaling; miR‐627/HMGB1 and RAGE/NF‐κB signaling formed a regulatory loop to modulate TGF‐β1‐induced PF in vitro. In conclusion, miR‐627 may be a potential agent that targets HMGB1 to inhibit its expression, thereby improving TGF‐β1‐induced PF in vitro.

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