Epigenetic histone methylation regulates transforming growth factor β-1 expression following bile duct ligation in rats

Shyr Ming Sheen-Chen, Chung Ren Lin, Kuan Hung Chen, Chien Hui Yang, Chien Te Lee, Hui Wen Huang, Chun Ying Huang

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: Multiple mechanisms contribute to the liver fibrosis following cholestasis. Recent research has focused on the role of transforming growth factor β-1 (TGF-β1) in the progression of fibrosis. The aim of our study is to examine the role of epigenetic chromatin marks, such as histone H3 lysine methylation (H3Kme), in bile duct ligation (BDL)-induced TGF-β1 gene expression in rat liver. Methods: Time course of methylated-histone H3 and SET7/9 recruitment were determined by chromatin immunoprecipitation in livers from BDL rats on days 1, 4, 9 and 14. Levels of TGF-β1 and SET7/9 were determined by western blots. The effect of SET7/9 knockdown on BDL-induced expression of TGF-β1, serum enzymes and liver collagen content was studied in vivo. Results: Results showed that BDL increased the expression of the TGF β-1. Increased levels of active chromatin marks (H3K4me1, H3K4me2, and H3K4me3) and decreased levels of repressive marks (H3K9me2 and H3K9me3) in TGF-β1 promoter accompanied the changes in expression of the TGF β-1. BDL also increased expression of the H3K4 methyltransferase SET7/9 and recruitment to the promoter. SET7/9 gene knockdown with siRNAs significantly attenuated BDL-induced TGF-β1 gene expression, serum enzymes and liver collagen content. Conclusions: Taken together, these results show the functional role of epigenetic chromatin histone H3Kme in BDL-induced TGF-β1 expression. Pharmacologic and other therapies that reverse these modifications could have potential hepatoprotective effects for BDL-induced cirrhosis.

Original languageEnglish
Pages (from-to)1285-1297
Number of pages13
JournalJournal of Gastroenterology
Volume49
Issue number8
DOIs
Publication statusPublished - Aug 2014
Externally publishedYes

Fingerprint

Transforming Growth Factors
Bile Ducts
Epigenomics
Histones
Methylation
Ligation
Chromatin
Liver
Fibrosis
Collagen
Gene Knockdown Techniques
Gene Expression
Chromatin Immunoprecipitation
Cholestasis
Methyltransferases
Enzymes
Serum
Liver Cirrhosis
Lysine
Western Blotting

Keywords

  • Cholestasis
  • Chromatin immunoprecipitation
  • Cirrhosis
  • SET7/9
  • siRNA

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Epigenetic histone methylation regulates transforming growth factor β-1 expression following bile duct ligation in rats. / Sheen-Chen, Shyr Ming; Lin, Chung Ren; Chen, Kuan Hung; Yang, Chien Hui; Lee, Chien Te; Huang, Hui Wen; Huang, Chun Ying.

In: Journal of Gastroenterology, Vol. 49, No. 8, 08.2014, p. 1285-1297.

Research output: Contribution to journalArticle

Sheen-Chen, Shyr Ming ; Lin, Chung Ren ; Chen, Kuan Hung ; Yang, Chien Hui ; Lee, Chien Te ; Huang, Hui Wen ; Huang, Chun Ying. / Epigenetic histone methylation regulates transforming growth factor β-1 expression following bile duct ligation in rats. In: Journal of Gastroenterology. 2014 ; Vol. 49, No. 8. pp. 1285-1297.
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abstract = "Background: Multiple mechanisms contribute to the liver fibrosis following cholestasis. Recent research has focused on the role of transforming growth factor β-1 (TGF-β1) in the progression of fibrosis. The aim of our study is to examine the role of epigenetic chromatin marks, such as histone H3 lysine methylation (H3Kme), in bile duct ligation (BDL)-induced TGF-β1 gene expression in rat liver. Methods: Time course of methylated-histone H3 and SET7/9 recruitment were determined by chromatin immunoprecipitation in livers from BDL rats on days 1, 4, 9 and 14. Levels of TGF-β1 and SET7/9 were determined by western blots. The effect of SET7/9 knockdown on BDL-induced expression of TGF-β1, serum enzymes and liver collagen content was studied in vivo. Results: Results showed that BDL increased the expression of the TGF β-1. Increased levels of active chromatin marks (H3K4me1, H3K4me2, and H3K4me3) and decreased levels of repressive marks (H3K9me2 and H3K9me3) in TGF-β1 promoter accompanied the changes in expression of the TGF β-1. BDL also increased expression of the H3K4 methyltransferase SET7/9 and recruitment to the promoter. SET7/9 gene knockdown with siRNAs significantly attenuated BDL-induced TGF-β1 gene expression, serum enzymes and liver collagen content. Conclusions: Taken together, these results show the functional role of epigenetic chromatin histone H3Kme in BDL-induced TGF-β1 expression. Pharmacologic and other therapies that reverse these modifications could have potential hepatoprotective effects for BDL-induced cirrhosis.",
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AU - Lee, Chien Te

AU - Huang, Hui Wen

AU - Huang, Chun Ying

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AB - Background: Multiple mechanisms contribute to the liver fibrosis following cholestasis. Recent research has focused on the role of transforming growth factor β-1 (TGF-β1) in the progression of fibrosis. The aim of our study is to examine the role of epigenetic chromatin marks, such as histone H3 lysine methylation (H3Kme), in bile duct ligation (BDL)-induced TGF-β1 gene expression in rat liver. Methods: Time course of methylated-histone H3 and SET7/9 recruitment were determined by chromatin immunoprecipitation in livers from BDL rats on days 1, 4, 9 and 14. Levels of TGF-β1 and SET7/9 were determined by western blots. The effect of SET7/9 knockdown on BDL-induced expression of TGF-β1, serum enzymes and liver collagen content was studied in vivo. Results: Results showed that BDL increased the expression of the TGF β-1. Increased levels of active chromatin marks (H3K4me1, H3K4me2, and H3K4me3) and decreased levels of repressive marks (H3K9me2 and H3K9me3) in TGF-β1 promoter accompanied the changes in expression of the TGF β-1. BDL also increased expression of the H3K4 methyltransferase SET7/9 and recruitment to the promoter. SET7/9 gene knockdown with siRNAs significantly attenuated BDL-induced TGF-β1 gene expression, serum enzymes and liver collagen content. Conclusions: Taken together, these results show the functional role of epigenetic chromatin histone H3Kme in BDL-induced TGF-β1 expression. Pharmacologic and other therapies that reverse these modifications could have potential hepatoprotective effects for BDL-induced cirrhosis.

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