单位：[1]Capital Med Univ, Beijing Chao Yang Hosp, Beijing Key Lab Resp & Pulm Circulat Disorders, Dept Resp & Crit Care Med,Beijing Inst Resp Med, Beijing 100020, Peoples R China北京朝阳医院[2]Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA[3]China Japan Friendship Hosp, Beijing, Peoples R China
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease. Although the pathogenesis is poorly understood, evidence suggests that genetic and epigenetic alterations, such as DNA methylation, may play a key role. Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGF-beta) superfamily and are important regulators in IPF. Here we identified BMP endothelial cell precursor-derived regulator (BMPER) as a key regulator of fibroblast activation. BMPER is a secreted glycoprotein that binds directly to BMPs and may regulate TGF-beta/BMP signaling, but its role in lung fibrosis is not clear. BMPER is highly expressed in human IPF lung fibroblasts compared to normal lung fibroblasts. Demethylation agent 5'-azacytidine decreased BMPER expression in fibroblasts, and attenuated the invasion and migration of IPF lung fibroblasts. Furthermore, siRNA-mediated reduction of BMPER in the human lung fibroblasts impaired cell migration and invasion. 5'-azacytidine treatment additionally regulated BMPER expression and reduced lung fibrosis in mice in vivo. These findings demonstrate that methylation of specific genes in fibroblasts may offer a new therapeutic strategy for IPF by modulating fibroblast activation.
基金：
NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P01 HL108793, R01 HL122068]; NATIONAL HEART, LUNG, AND BLOOD INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01HL122068, P01HL108793] Funding Source: NIH RePORTER
第一作者单位：[1]Capital Med Univ, Beijing Chao Yang Hosp, Beijing Key Lab Resp & Pulm Circulat Disorders, Dept Resp & Crit Care Med,Beijing Inst Resp Med, Beijing 100020, Peoples R China[2]Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA
通讯作者：
推荐引用方式(GB/T 7714)：
Huan Caijuan,Yang Ting,Liang Jiurong,et al.Methylation-mediated BMPER expression in fibroblast activation in vitro and lung fibrosis in mice in vivo[J].SCIENTIFIC REPORTS.2015,5:doi:10.1038/srep14910.
APA：
Huan, Caijuan,Yang, Ting,Liang, Jiurong,Xie, Ting,Cheng, Luis...&Jiang, Dianhua.(2015).Methylation-mediated BMPER expression in fibroblast activation in vitro and lung fibrosis in mice in vivo.SCIENTIFIC REPORTS,5,
MLA：
Huan, Caijuan,et al."Methylation-mediated BMPER expression in fibroblast activation in vitro and lung fibrosis in mice in vivo".SCIENTIFIC REPORTS 5.(2015)
