Metformin ameliorates bleomycin-induced pulmonary fibrosis in mice by suppressing IGF-1

Huijuan Xiao; Xiaoxi Huang; Shiyao Wang; Zheng Liu; Run Dong; Dingyun Song; Huaping Dai

Metformin ameliorates bleomycin-induced pulmonary fibrosis in mice by suppressing IGF-1

Am J Transl Res. 2020 Mar 15;12(3):940-949. eCollection 2020.

Authors

Huijuan Xiao^{1

2

3

4}, Xiaoxi Huang⁵, Shiyao Wang^{2

3

4}, Zheng Liu⁵, Run Dong⁶, Dingyun Song^{2

3

4}, Huaping Dai^{1

2

3

4}

Affiliations

¹ Department of Respiratory Medicine, Capital Medical University Beijing 100054, P. R. China.
² Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital Beijing 100029, P. R. China.
³ National Clinical Research Center for Respiratory Diseases Beijing 100029, P. R. China.
⁴ Institute of Respiratory Medicine, Chinese Academy of Medical Sciences Beijing 100029, P. R. China.
⁵ Department of Medical Research, Beijing Chao-Yang Hospital, Capital Medical University Beijing 100020, P. R. China.
⁶ Department of Respiratory Medicine, Zhengzhou Central Hospital Zhengzhou, P. R. China.

PMID: 32269725
PMCID: PMC7137034

Abstract

Idiopathic pulmonary fibrosis (IPF) is a devastating disease, which is characterized by the progressive deterioration in lung function. In the pathogenesis of IPF, insulin-like growth factor-1 (IGF-1) has been found to be heavily involved. Metformin, a commonly used oral antidiabetic agent, is known to inhibit IGF-1 by the reversal of hyperinsulinemia. In this study, we evaluated the effects of metformin in pulmonary fibrosis in C57/BL6J mice, and further understand the role of IGF-1 signaling pathway involving in this process. Pulmonary fibrosis was induced experimentally in these mice by the intratracheal injection of bleomycin (BLM). Metformin was given orally the day before or 14 days after bleomycin injection, while pirfenidone was used as the positive control. Our study showed that intratracheal injection of bleomycin induced pulmonary fibrosis in mice, with observed elevation in collagen, fibronectin and α-SMA level, characterized by the enhanced IGF-1 and PI3K expression. Metformin was able to inhibit these effects significantly, and its antifibrotic effect had no marked difference with pirfenidone. Our results show that metformin attenuates bleomycin-induced pulmonary fibrosis via IGF-1 pathway.

Keywords: IGF-1; Pulmonary fibrosis; bleomycin; metformin; murine model.