Cargando…

Methylation-mediated BMPER expression in fibroblast activation in vitro and lung fibrosis in mice in vivo

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Huan, Caijuan, Yang, Ting, Liang, Jiurong, Xie, Ting, Cheng, Luis, Liu, Ningshan, Kurkciyan, Adrianne, Monterrosa Mena, Jessica, Wang, Chen, Dai, Huaping, Noble, Paul W., Jiang, Dianhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4595647/
https://www.ncbi.nlm.nih.gov/pubmed/26442443
http://dx.doi.org/10.1038/srep14910
_version_ 1782393645288128512
author Huan, Caijuan
Yang, Ting
Liang, Jiurong
Xie, Ting
Cheng, Luis
Liu, Ningshan
Kurkciyan, Adrianne
Monterrosa Mena, Jessica
Wang, Chen
Dai, Huaping
Noble, Paul W.
Jiang, Dianhua
author_facet Huan, Caijuan
Yang, Ting
Liang, Jiurong
Xie, Ting
Cheng, Luis
Liu, Ningshan
Kurkciyan, Adrianne
Monterrosa Mena, Jessica
Wang, Chen
Dai, Huaping
Noble, Paul W.
Jiang, Dianhua
author_sort Huan, Caijuan
collection PubMed
description 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-β (TGF-β) 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-β/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.
format Online
Article
Text
id pubmed-4595647
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-45956472015-10-13 Methylation-mediated BMPER expression in fibroblast activation in vitro and lung fibrosis in mice in vivo Huan, Caijuan Yang, Ting Liang, Jiurong Xie, Ting Cheng, Luis Liu, Ningshan Kurkciyan, Adrianne Monterrosa Mena, Jessica Wang, Chen Dai, Huaping Noble, Paul W. Jiang, Dianhua Sci Rep Article 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-β (TGF-β) 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-β/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. Nature Publishing Group 2015-10-07 /pmc/articles/PMC4595647/ /pubmed/26442443 http://dx.doi.org/10.1038/srep14910 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Huan, Caijuan
Yang, Ting
Liang, Jiurong
Xie, Ting
Cheng, Luis
Liu, Ningshan
Kurkciyan, Adrianne
Monterrosa Mena, Jessica
Wang, Chen
Dai, Huaping
Noble, Paul W.
Jiang, Dianhua
Methylation-mediated BMPER expression in fibroblast activation in vitro and lung fibrosis in mice in vivo
title Methylation-mediated BMPER expression in fibroblast activation in vitro and lung fibrosis in mice in vivo
title_full Methylation-mediated BMPER expression in fibroblast activation in vitro and lung fibrosis in mice in vivo
title_fullStr Methylation-mediated BMPER expression in fibroblast activation in vitro and lung fibrosis in mice in vivo
title_full_unstemmed Methylation-mediated BMPER expression in fibroblast activation in vitro and lung fibrosis in mice in vivo
title_short Methylation-mediated BMPER expression in fibroblast activation in vitro and lung fibrosis in mice in vivo
title_sort methylation-mediated bmper expression in fibroblast activation in vitro and lung fibrosis in mice in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4595647/
https://www.ncbi.nlm.nih.gov/pubmed/26442443
http://dx.doi.org/10.1038/srep14910
work_keys_str_mv AT huancaijuan methylationmediatedbmperexpressioninfibroblastactivationinvitroandlungfibrosisinmiceinvivo
AT yangting methylationmediatedbmperexpressioninfibroblastactivationinvitroandlungfibrosisinmiceinvivo
AT liangjiurong methylationmediatedbmperexpressioninfibroblastactivationinvitroandlungfibrosisinmiceinvivo
AT xieting methylationmediatedbmperexpressioninfibroblastactivationinvitroandlungfibrosisinmiceinvivo
AT chengluis methylationmediatedbmperexpressioninfibroblastactivationinvitroandlungfibrosisinmiceinvivo
AT liuningshan methylationmediatedbmperexpressioninfibroblastactivationinvitroandlungfibrosisinmiceinvivo
AT kurkciyanadrianne methylationmediatedbmperexpressioninfibroblastactivationinvitroandlungfibrosisinmiceinvivo
AT monterrosamenajessica methylationmediatedbmperexpressioninfibroblastactivationinvitroandlungfibrosisinmiceinvivo
AT wangchen methylationmediatedbmperexpressioninfibroblastactivationinvitroandlungfibrosisinmiceinvivo
AT daihuaping methylationmediatedbmperexpressioninfibroblastactivationinvitroandlungfibrosisinmiceinvivo
AT noblepaulw methylationmediatedbmperexpressioninfibroblastactivationinvitroandlungfibrosisinmiceinvivo
AT jiangdianhua methylationmediatedbmperexpressioninfibroblastactivationinvitroandlungfibrosisinmiceinvivo