Transforming growth factor β1 induces the expression of collagen type I by DNA methylation in cardiac fibroblasts.

Transforming growth factor-beta (TGF-β), a key mediator of cardiac fibroblast activation, has a major influence on collagen type I production. However, the epigenetic mechanisms by which TGF-β induces collagen type I alpha 1 (COL1A1) expression are not fully understood. This study was designed to ex...

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Autores principales:	Xiaodong Pan, Zhongpu Chen, Rong Huang, Yuyu Yao, Genshan Ma
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/05a7662add64430fa4d1950a5762781e
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spelling	oai:doaj.org-article:05a7662add64430fa4d1950a5762781e2021-11-18T07:51:11ZTransforming growth factor β1 induces the expression of collagen type I by DNA methylation in cardiac fibroblasts.1932-620310.1371/journal.pone.0060335https://doaj.org/article/05a7662add64430fa4d1950a5762781e2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23560091/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Transforming growth factor-beta (TGF-β), a key mediator of cardiac fibroblast activation, has a major influence on collagen type I production. However, the epigenetic mechanisms by which TGF-β induces collagen type I alpha 1 (COL1A1) expression are not fully understood. This study was designed to examine whether or not DNA methylation is involved in TGF-β-induced COL1A1 expression in cardiac fibroblasts. Cells isolated from neonatal Sprague-Dawley rats were cultured and stimulated with TGF-β1. The mRNA levels of COL1A1 and DNA methyltransferases (DNMTs) were determined via quantitative polymerase chain reaction and the protein levels of collagen type I were determined via Western blot as well as enzyme-linked immunosorbent assay. The quantitative methylation of the COL1A1 promoter region was analyzed using the MassARRAY platform of Sequenom. Results showed that TGF-β1 upregulated the mRNA expression of COL1A1 and induced the synthesis of cell-associated and secreted collagen type I in cardiac fibroblasts. DNMT1 and DNMT3a expressions were significantly downregulated and the global DNMT activity was inhibited when treated with 10 ng/mL of TGF-β1 for 48 h. TGF-β1 treatment resulted in a significant reduction of the DNA methylation percentage across multiple CpG sites in the rat COL1A1 promoter. Thus, TGF-β1 can induce collagen type I expression through the inhibition of DNMT1 and DNMT3a expressions as well as global DNMT activity, thereby resulting in DNA demethylation of the COL1A1 promoter. These findings suggested that the DNMT-mediated DNA methylation is an important mechanism in regulating the TGF-β1-induced COL1A1 gene expression.Xiaodong PanZhongpu ChenRong HuangYuyu YaoGenshan MaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e60335 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaodong Pan Zhongpu Chen Rong Huang Yuyu Yao Genshan Ma Transforming growth factor β1 induces the expression of collagen type I by DNA methylation in cardiac fibroblasts.
description	Transforming growth factor-beta (TGF-β), a key mediator of cardiac fibroblast activation, has a major influence on collagen type I production. However, the epigenetic mechanisms by which TGF-β induces collagen type I alpha 1 (COL1A1) expression are not fully understood. This study was designed to examine whether or not DNA methylation is involved in TGF-β-induced COL1A1 expression in cardiac fibroblasts. Cells isolated from neonatal Sprague-Dawley rats were cultured and stimulated with TGF-β1. The mRNA levels of COL1A1 and DNA methyltransferases (DNMTs) were determined via quantitative polymerase chain reaction and the protein levels of collagen type I were determined via Western blot as well as enzyme-linked immunosorbent assay. The quantitative methylation of the COL1A1 promoter region was analyzed using the MassARRAY platform of Sequenom. Results showed that TGF-β1 upregulated the mRNA expression of COL1A1 and induced the synthesis of cell-associated and secreted collagen type I in cardiac fibroblasts. DNMT1 and DNMT3a expressions were significantly downregulated and the global DNMT activity was inhibited when treated with 10 ng/mL of TGF-β1 for 48 h. TGF-β1 treatment resulted in a significant reduction of the DNA methylation percentage across multiple CpG sites in the rat COL1A1 promoter. Thus, TGF-β1 can induce collagen type I expression through the inhibition of DNMT1 and DNMT3a expressions as well as global DNMT activity, thereby resulting in DNA demethylation of the COL1A1 promoter. These findings suggested that the DNMT-mediated DNA methylation is an important mechanism in regulating the TGF-β1-induced COL1A1 gene expression.
format	article
author	Xiaodong Pan Zhongpu Chen Rong Huang Yuyu Yao Genshan Ma
author_facet	Xiaodong Pan Zhongpu Chen Rong Huang Yuyu Yao Genshan Ma
author_sort	Xiaodong Pan
title	Transforming growth factor β1 induces the expression of collagen type I by DNA methylation in cardiac fibroblasts.
title_short	Transforming growth factor β1 induces the expression of collagen type I by DNA methylation in cardiac fibroblasts.
title_full	Transforming growth factor β1 induces the expression of collagen type I by DNA methylation in cardiac fibroblasts.
title_fullStr	Transforming growth factor β1 induces the expression of collagen type I by DNA methylation in cardiac fibroblasts.
title_full_unstemmed	Transforming growth factor β1 induces the expression of collagen type I by DNA methylation in cardiac fibroblasts.
title_sort	transforming growth factor β1 induces the expression of collagen type i by dna methylation in cardiac fibroblasts.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/05a7662add64430fa4d1950a5762781e
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Transforming growth factor β1 induces the expression of collagen type I by DNA methylation in cardiac fibroblasts.

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