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  The Histone Methyltransferase Suv39h2 Contributes to Nonalcoholic Steatohepatitis in Mice

Fan, Z., Li, L., Li, M., Zhang, X., Hao, C., Yu, L., et al. (2017). The Histone Methyltransferase Suv39h2 Contributes to Nonalcoholic Steatohepatitis in Mice. Hepatology, 65, 1904. doi:10.1002/hep.29127.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-C157-4 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-C23D-C
Genre: Journal Article

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 Creators:
Fan, Zhiwen1, Author
Li, Luyang1, Author
Li, Min1, Author
Zhang, Xinjian1, Author
Hao, Chenzhi1, Author
Yu, Liming1, Author
Zeng, Sheng1, Author
Xu, Huihui1, Author
Fang, Mingming1, Author
Shen, Aiguo1, Author
Jenuwein, Thomas2, Author              
Xu, Yong1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              

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 Abstract: Uncontrolled inflammatory response highlights the central theme of nonalcoholic steatohepatitis (NASH), a growing global pandemic. Hepatocytes and macrophages represent two major sources of hepatic inflammation during NASH pathogenesis, contributing to excessive synthesis of proinflammatory mediators. The epigenetic mechanism that accounts for the activation of hepatocytes and macrophages in this process remains obscure. Here, we report that compared to wild-type littermates, mice with a deficiency in the histone H3K9 methyltransferase suppressor of variegation 39 homolog 2 (Suv39h2, knockout) exhibited a less severe form of NASH induced by feeding with a high-fat, high-carbohydrate diet. Pro-NASH stimuli increased Suv39h2 expression in cell culture, in mice, and in human livers. In hepatocytes, Suv39h2 bound to the Sirt1 gene promoter and repressed Sirt1 transcription. Suv39h2 deficiency normalized Sirt1 expression, allowing nuclear factor kappa B/p65 to become hypoacetylated and thus dampening nuclear factor kappa B–dependent transcription of proinflammatory mediators. In macrophages, Suv39h2-mediated repression of peroxisome proliferator–activated receptor gamma transcription favored a proinflammatory M1 phenotype over an anti-inflammatory M2 phenotype, thereby elevating hepatic inflammation. Conclusion: Suv39h2 plays a pivotal role in the regulation of inflammatory response in hepatocytes and macrophages, contributing to NASH pathogenesis.

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Language(s): eng - English
 Dates: 2017-06
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: DOI: 10.1002/hep.29127
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Title: Hepatology
Source Genre: Journal
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Publ. Info: Philadelphia, PA : No longer published by Elsevier now AASLD
Pages: - Volume / Issue: 65 Sequence Number: - Start / End Page: 1904 Identifier: ISSN: 0270-9139
CoNE: https://pure.mpg.de/cone/journals/resource/954925502190