Screening of DNA methylation sites and construction of differential methylation profiles in human hepatic stellate cells fibrosis and autophagy induced by sodium arsenite
10.3760/cma.j.cn231583-20220424-00134
- VernacularTitle:亚砷酸钠致人肝星状细胞纤维化及自噬中DNA甲基化位点筛查及差异甲基化谱构建
- Author:
Fei HUANG
1
;
Yaermaimaiti DILINAER
;
Guanxin DING
;
Lijun ZHAO
;
Jing ZHOU
;
Shunhua WU
Author Information
1. 新疆医科大学公共卫生学院，乌鲁木齐 830011
- Keywords:
Arsenites;
Human hepatic stellate cells;
Liver fibrosis;
Autophagy;
DNA methylation
- From:
Chinese Journal of Endemiology
2023;42(1):11-16
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze DNA methylation sites related to fibrosis and autophagy in human hepatic stellate cells (LX-2 cells) induced by sodium arsenite (NaAsO 2), and to screen specific methylation genes related to fibrosis and autophagy. Methods:Genome-wide DNA detection was performed using Illumina Infinium Methylation EPIC BeadChips (850K methylation chip) to derive differential methylation sites in LX-2 cells (control group) and the fibrosis and autophagy models of LX-2 cells induced by NaAsO 2(low, medium and high dose groups: the final concentrations were 5, 10, 15 μmol/L NaAsO 2, respectively, after 48 h intervention). Gene ontology (GO) function enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis were used to explore gene function. Results:The model of cell fibrosis and autophagy was established successfully in high dose group. The results of 850K methylation chip detection showed that there were 25 817 significant different methylation sites between the high dose group and the control group, including 12 083 hypermethylation sites and 13 734 hypomethylation sites. GO function enrichment analysis showed that the molecular functions of differentially methylated genes mainly included protein binding, ion binding, catalytic activity, enzyme binding. KEGG signaling pathway enrichment analysis showed that the pathways involved in differentially methylated genes mainly included metabolic pathway, cancer pathway, phosphatidylinositol-3-kinase-protein kinase B (PI3K-Akt) signaling pathway, endocytosis, and mitogen activated protein kinase (MAPK) signaling pathway. In the promoter region, 11 and 29 differentially methylated genes related to fibrosis and autophagy were screened, respectively.Conclusions:A large number of differential methylation sites exist in the process of NaAsO 2 induced fibrosis and autophagy of LX-2 cells. Specific methylation genes related to fibrosis and autophagy are screened out.
