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Effect of maternal methyl donor deficient diet on experimental colitis in rat offsprings

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Author:
No author available
Journal Title:
World Chinese Journal of Digestology
Issue:
31
DOI:
10.11569/wcjd.v25.i31.2791
Key Word:
溃疡性结肠炎;甲基供体;基因甲基化;干扰素γ;Ulcerative colitis;Methyl donor;DNA methylation;Interferon-γ

Abstract´╝Ü AIM To investigate whether maternal methyl donor deficiency promotes the pathogenesis and development of ulcerative colitis (UC) by affecting DNA methylation.METHODS Maternal BALB/c mice were fed either a normal diet (C) or a methyl donor deficiency diet (D) from one month before pregnancy until the offspring weaned.Young mice were given dextran sulfate sodium (DSS) or purified water as drink water for five days.The young mice were randomly divided into four groups:C/DSS-,D/DSS-,C/DSS+,and D/DSS+.The degree of colonic inflammation was evaluated;serum folate,vitamin B12,and homocysteine (Hcy) were determined;the expression of interferon-γ(IFN-γ) in the colonic mucosa was detected;and the methylation level of CpG islands in the IFNG promoter was determined.RESULTS The disease activity index (DAI) was significantly higher in the D/DSS+ group than in the C/DSS+group (3.22 ± 0.55 vs 2.22 ± 0.50,P < 0.01).Compared to the normal diet group,the methyl donor deficient diet group had significantly lower serum levels of folic acid (8.87nmol/L ± 1.11 nmol/L vs 11.34 nmol/L ± 0.31nmol/L,P < 0.01) and vitamin B12 (409.2 ng/L± 56.27 ng/L vs 676.1 ng/L ± 1.66 ng/L,P < 0.01)and significantly higher Hcy (8.45 μmol/L ± 0.35μrmol/L vs 6.77 μmol/L ± 0.36 μmol/L,P < 0.01).The IFN-γ expression in the colonic mucosa was significantly higher in the C/DSS+ and D/DSS+ groups than in the C/DSS-and D/DSS-groups (5.3 ± 1.2 vs 10.6 ± 10.8,x2=14.517,P < 0.01).The expression level of IFN-γ in the colonic mucosa of DSS+ groups was positively related to the degree of inflammation (r =0.853,0.840;P =0.031,0.036;P < 0.05).There were no significant differences in the methylation level of all CpG sites or same CpG sites among the four samples.CONCLUSION Methyl donor deficient diet may cause aggravated experimental colitis by increasing the expression of IFN-γ.The abnormal expression of IFN-γ in the colonic mucosa has no relationship with hypo-methylation of CpG islands in the IFNG promoter.

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