Page 43
conferenceseries
.com
Volume 7, Issue 5 (Suppl)
J Clin Exp Pathol
ISSN: 2161-0681 JCEP, an open access journal
Pathology Congress 2017
November 13-14, 2017
NOVEMBER 13-14, 2017 OSAKA, JAPAN
14
th
Asia Pacific Pathology Congress
The histone methyl-transferase Suv39h2 contributes to non-alcoholic steatohepatitis in mice
Zhiwen Fan
Nanjing University, China
U
ncontrolled inflammatory response highlights the central theme of Non-Alcoholic Steatohepatitis (NASH), a growing
global pandemic. Hepatocytes and macrophages represent two major sources of hepatic inflammation during NASH
pathogenesis contributing to excessive synthesis of pro-inflammatory 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
(WT) littermates, mice with a deficiency in the histone H3K9 methyl-transferase Suv39h2 (KO) exhibited a less severe form
of NASH induced by feeding with High-Fat high-carbohydrate Diet (HFD). 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 allowingNF-κB/p65 to become hypo-acetylated thus dampening
NF-κB-dependent transcription of pro-inflammatory mediators. In macrophages, Suv39h2-mediated repression of PPARγ
transcription favored a pro-inflammatory M1 phenotype over an anti-inflammatory M2 phenotype thereby elevating hepatic
inflammation. It can be concluded that Suv39h2 plays a pivotal role in the regulation of inflammatory response in hepatocytes
and macrophages contributing to NASH pathogenesis.
Biography
Zhiwen Fan has completed his MD degree in Nanjing Medical University in 2016 and currently working as the Director of Molecular Pathology Laboratory at Nanjing
Drum Tower Hospital. His research field is majorly in the study of liver disease related transcriptional regulation, which was mainly through Post-Translational
Modification (PTM) mediated fine tuning of transcription factors. He is the author of over 13 papers in reputed journals.
fanzhiwenfff@126.comZhiwen Fan, J Clin Exp Pathol 2017, 7:5 (Suppl)
DOI: 10.4172/2161-0681-C1-041