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...
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Nature Publishing Group
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4595647/ |
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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 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/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| 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 |
| spellingShingle |
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 |
| 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 |
| title |
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_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_sort |
methylation-mediated bmper expression in fibroblast activation in vitro and lung fibrosis in mice in vivo |
| 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. |
| publisher |
Nature Publishing Group |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4595647/ |
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1613484302882832384 |