Effects of bone morphogenetic protein 4 on TGF-β1-induced cell proliferation, apoptosis, activation and differentiation in mouse lung fibroblasts via ERK/p38 MAPK signaling pathway

Author:

Cai Zhou12,Guo Hua1,Qian Jing13,Liu Wei1,Li Yuanyuan1,Yuan Liang1,Zhou You1,Lin Ran1,Xie Xiaohui1,Yang Qiong3,Wu Guoying3,Li Qiongqiong1,Zhao Li1,Liu Fei1,Wang Jian1,Lu Wenju1

Affiliation:

1. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China

2. Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China

3. Key Laboratory of National Health Commission for the Diagnosis & Treatment of COPD, The People’s Hospital of Inner Mongolia Autonomous Region, Hohhot, Inner Mongolia, China

Abstract

Fibroblasts, in particular myofibroblasts, are the critical effector cells in idiopathic pulmonary fibrosis (IPF), a deadly lung disease characterized by abnormal lung remodeling and the formation of “fibroblastic foci”. Aberrant activation of TGF-β1 is frequently encountered and promotes fibroblast proliferation, activation, and differentiation in pulmonary fibrosis. Hence, the inhibition of TGF-β1-induced lung fibroblast activation holds promise as a therapeutic strategy for IPF. The present study aimed to investigate the potential effect and underlying mechanisms of bone morphogenetic protein 4 (BMP4) on TGF-β1-induced proliferation, apoptosis, activation and myofibroblast differentiation of adult lung fibroblasts. Here, we demonstrated that BMP4 expression was significantly decreased in TGF-β1-stimulated mouse primary lung fibroblasts (PLFs). BMP4 inhibited proliferation and apoptosis resistance of TGF-β1-stimulated mouse PLFs. BMP4 suppressed TGF-β1-induced fibroblast activation and differentiation in mouse PLFs. We also found that BMP4 inhibited TGF-β1-induced ERK and p38 MAPK phosphorylation. Our findings indicate that BMP4 exerts its anti-fibrotic effects by regulating fibroblast proliferation, apoptosis, activation and differentiation via the inhibition of the ERK/p38 MAPK signaling pathway, and thus has a potential for the treatment of pulmonary fibrosis.

Funder

National Key R&D Project

National Natural Science Foundation of China

Guangzhou Municipal Science and Technology grants

Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program

Changjiang Scholars and Innovative Research Team in University

Publisher

PeerJ

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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