Fig. 1: Upregulation of hepatic MCM7 expression driven by YAP activation in liver fibrosis.

A, BMcm7 transcript levels were assessed using two in-house RNA-seq data obtained from fibrotic mouse liver tissues following 8-week S. japonicum infection (A) or 8-week CCl4 treatment (B). C, D Immunohistochemical (IHC) analysis was performed to evaluate MCM7 expression were assessed in fibrotic liver tissues from mice infected with S. japonicum (C) or treated with CCl4 (D) for 4, 6, and 8 weeks (scale bar: 50 μm), with quantification of MCM7⁺ staining shown in the corresponding graphs. E–G MCM7 expression levels in human liver tissue samples from normal (n = 3) and cirrhosis (n = 3) groups, were assessed by IHC (E) (scale bar: 100 μm), with the graph showing the area of MCM7⁺ staining, Western blot (F) displaying protein levels, and qRT-PCR (G) determining mRNA expression. H Immunofluorescence (IF) analysis was performed to assess the colocalization of MCM7 in fibrotic liver sections from mice infected with S. japonicum for 8 weeks, with albumin (ALB), α-SMA, and F4/80 used to mark hepatocytes (HCs), hepatic stellate cells (HSCs), and Kupffer cells (KCs), respectively. Nuclei were stained with DAPI (scale bar: 50 μm). I, J MCM7 expression levels were assessed in primary hepatocytes (PHCs) isolated from uninfected mice and mice infected with S. japonicum for 8 weeks by Western blot (I), with the graph displaying protein levels, and by qRT-PCR (J). K, L Detection of protein (K) and mRNA (L) levels of MCM7 in PHCs after XMU-MP-1 stimulation for 24 h. M, N Detection of protein (M) and mRNA (N) levels of YAP and MCM7 in HepG2 cells transfected with shYAP. O The schematic diagram shows the MCM7 promoter region with YAP binding sites, and relative luciferase activity of the MCM7 promoter in HEK293T cells transfected with shYAP and pHAGE-YAP or pHAGE-YAP^5SA. P Relative luciferase activity of the MCM7 promoter in HEK293T cells transfected with pHAGE-YAP or pHAGE-YAP^5SA, with or without mutations in the YAP binding site. Data are expressed as the mean ± SD of 3–6 mice per group and are representative of three independent experiments. Statistical analyses were performed using unpaired Student’s t-test or one-way ANOVA. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; ns not significant.