10.3389/fphar.2018.00553.s003
Xue-yin Pan
Xue-yin
Pan
Yang Yang
Yang
Yang
Hong-wu Meng
Hong-wu
Meng
Hai-di Li
Hai-di
Li
Xin Chen
Xin
Chen
Hui-min Huang
Hui-min
Huang
Fang-tian Bu
Fang-tian
Bu
Hai-xia Yu
Hai-xia
Yu
Qin Wang
Qin
Wang
Cheng Huang
Cheng
Huang
Xiao-ming Meng
Xiao-ming
Meng
Jun Li
Jun
Li
Image_3_DNA Methylation of PTGIS Enhances Hepatic Stellate Cells Activation and Liver Fibrogenesis.TIF
Frontiers
2018
DNA methylation
gene expression
proliferation
apoptosis
hepatic stellate cells
PTGIS
2018-05-28 14:08:49
Figure
https://frontiersin.figshare.com/articles/figure/Image_3_DNA_Methylation_of_PTGIS_Enhances_Hepatic_Stellate_Cells_Activation_and_Liver_Fibrogenesis_TIF/6376667
<p>The activation of hepatic stellate cells (HSCs) is a central event in the progression of liver fibrosis. Multiple studies proved that DNA methylation might accelerate HSCs activation. However, the specific pathogenesis of liver fibrosis remains not fully addressed. Our laboratory performed Genome methylation screening to find out the methylated gene in mice with liver fibrosis. The pilot experiments showed that the promoter of prostacyclin synthase (PTGIS) gene was hypermethylated in CCl<sub>4</sub>-induced liver fibrosis mouse model. Moreover, the down-regulated PTGIS expression can be restored by DNMTs-RNAi and 5-aza-2-deoxycytidine (5-azadC), an inhibitor of DNA methyltransferase (DNMTs). Methylation-specific PCR (MSP) showed that the methylation status of PTGIS in HSC-T6 cells cultures with TGF-β1 (10 ng/mL) was elevated compared with control group. Chromatin immunoprecipitation (ChIP) assay indicated that PTGIS methylation was mainly induced by DNMT1 and DNMT3b. We further investigated the function of PTGIS in liver fibrosis by Recombinant Hepatic-adeno-associated virus (rAAV8)-PTGIS overexpression. The data indicated that overexpression of PTGIS in mouse liver accompanied by elevated apoptosis-related proteins expression in primary HSCs. Conversely, PTGIS silencing mediated by RNAi enhanced the expression of α-SMA and COL1a1 in vitro. Those results illustrated that adding PTGIS expression inhibits the activation of HSCs and alleviates liver fibrosis. Therefore, our study unveils the role of PTGIS in HSCs activation, which may provide a possible explanation for CCl<sub>4</sub>-mediated liver fibrosis.</p>