Analysis of DNA methylation with 5-Azac induced immune hyporesponsiveness following acute graft-versus-host disease
10.11958/20150153
- VernacularTitle:5-Azac诱导急性移植物抗宿主病免疫低反应的甲基化研究
- Author:
Xiaoning ZHANG
;
Yuxia ZHAO
;
Jianhai WANG
;
Xuhong MIAO
;
Keqiu LI
;
Guang LI
- Publication Type:Journal Article
- Keywords:
graft vs host disease;
methylation;
5-azacytidine;
MeDIP-seq;
immune hyporesponsiveness
- From:
Tianjin Medical Journal
2016;44(2):173-177
- CountryChina
- Language:Chinese
-
Abstract:
Objective To analyse the change of DNA methylation with 5-Azac injection in acute graft-versus-host dis- ease (aGVHD) mouse model, which received allogeneic bone marrow transplantation, and explore the immunomodulatory ef-fects of 5-Azac. Methods Male C57BL/6 (H-2b)and female BALB/c (H-2d) mice were selected as donor and recipient of complete allotransplantation. BABL/c mice were divided into two groups, transplantation control group and 5-Azac experi-mental group. At 1-7, 14, 21 and 28-day after transplantion, 5-Azac 0.25 mg/kg (0.3 mL/time) was injected by tail vein in experimental group, while the control group were injected with sterile water 0.3 mL/time. Peripheral blood DNA samples were collected from three control mice and three experimental mice, then mixed with equal amount respectively. The MeDIP-seq method was selected to detect methylation changes in mice, and the differential DNA methylation in the biological path-ways was analyzed. Results The survival time was prolonged, and the rejection reaction was decreased in 5-Azac experi-mental group, which suggested immune hyporesponsiveness post aGVHD. The MeDIP-seq result showed that 369 different DNA methylation located in the promoter regions, including 239 up-regulated genes and 130 down-regulated genes. There were 184 differential DNA methylation genes located in the exon regions, including 113 up-regulated genes and 71 down-regulated genes. Differential DNA methylation genes involved in 10 immunological signaling pathways, respectively. Among them, TGF-β, GSK-3β, SYK, PI3K, NFAT, CD28 andα4β7 were closely related to the development of aGVHD. Conclu-sion 5-Azac can effectively induce immune hyporesponsiveness post aGVHD by changing the gene methylation status.
