NOGO-B promotes EMT in lung fibrosis via MMP14 mediates free TGF-beta1 formation

Ye Xiong; Jing Zhang; Lingzhi Shi; Yunye Ning; Ying Zhu; Si Chen; Meng Yang; Jingyu Chen; Guo-Wu Zhou; Qiang Li

doi:10.18632/oncotarget.20297

NOGO-B promotes EMT in lung fibrosis via MMP14 mediates free TGF-beta1 formation

Oncotarget. 2017 Aug 16;8(41):71024-71037. doi: 10.18632/oncotarget.20297. eCollection 2017 Sep 19.

Authors

Ye Xiong¹, Jing Zhang², Lingzhi Shi^{3

4}, Yunye Ning¹, Ying Zhu¹, Si Chen¹, Meng Yang¹, Jingyu Chen⁴, Guo-Wu Zhou^{1

5}, Qiang Li^{1

6}

Affiliations

¹ Department of Respiratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China.
² Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China.
³ Department of Respiratory Medicine, Wuxi People Hospital, Nanjing Medical University, Nanjing, China.
⁴ Jiangsu Province Key Laboratory of Organ Transplantation, Wuxi People Hospital, Nanjing Medical University, Nanjing, China.
⁵ National Clinical Research Center for Respiratory Diseases, Center for Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China.
⁶ Department of Respiratory Medicine, Shanghai First Hospital, Shanghai Jiaotong University, Shanghai, China.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a lung disease with an extremely poor prognosis. Epithelial mesenchymal transition (EMT) appearing on the airway epithelial cell plays an essential role in the formation and development of Idiopathic pulmonary fibrosis. In this paper, Bleomycin (BLM)-induced mice model combined with bioinformatics analysis were employed to elucidate the potential mechanism of EMT in pulmonary fibrosis. The obtained results showed that endoplasmic reticulum protein Nogo-b may promote MMP14-mediated proprotein maturation of TGF-β1, accelerating the release of free TGF-β1 in type II airway epithelial cells A549, subsquently, induce the epithelial-mesenchymal transition (EMT) of the cell. In all, the overexpression of Nogo-b play a role in the course of pulmonary fibrosis by influencing the EMT ability of cells.

Keywords: MMP14; Nogo-b; TGF-beta1; epithelial mesenchymal transition (EMT); idiopathic pulmonary fibrosis (IPF).