Fig 1.
XPO4 expression is silenced through DNA hypermethylation in fibrosis.
a) Increased hepatic XPO4 DNA methylation in patients with MAFLD and b-d) in three mouse models CCl4, BDL and MCD. e) Hepatic Xpo4 mRNA expression is negatively correlated with Xpo4 DNA methylation in the mouse models. The results are presented as the mean value ± SEM. The statistical significance of the observed differences between groups was assessed by using the unpaired two-sample Student’s t-test. The significance levels used in this study were denoted as follows: *P < 0.05, ** P<0.01, *** P<0.001.
Fig 2.
a) The hepatic mRNA expression of DNA methyltransferases (DNMTs), DNMT1, DNMT3a, and DNMT3b, the enzymes that result in DNA methylation is upregulated in patients with MAFLD-fibrosis compared to healthy group and b) in bile duct ligation (BDL) compared to sham. c) Representative expression pattern of XPO4, DNMT1, DNMT3a, and DNMT3b in livers from mice with bile duct ligation (BDL) and sham (n = 3 per group). Original magnification: 200×; and the intensity of expression was quantified digitally using ImageJ. d) Correlation between DNMTs and XPO4 expression was assessed by Spearman’s rank correlation. e) TGFβ1 increases DNMTs in LX-2 cells. f) 5-Aza decreases DNMTs mRNA expression in HSCs. g) 5-Aza increases XPO4 gene expression in HSCs. h) Specific siRNAs for these DNMTs in LX-2 cells led to increased XPO4 expression. The results are presented as the mean value ± SEM. The statistical significance of the observed differences between groups was assessed by using the unpaired two-sample Student’s t-test. The significance levels used in this study were denoted as follows: *P < 0.05, ** P<0.01, *** P<0.001.
Fig 3.
XPO4 CNV is not associated with XPO4 DNA methylation.
The outcomes are presented in the form of the mean value plus or minus the SEM. The statistical significance of the observed differences between groups was determined by using the one-way ANOVA method.