Fig. 2: Deletion of SENP1 in hepatocytes causes RIPK1-driven inflammation, steatosis, and fibrosis.
From: SENP1 prevents steatohepatitis by suppressing RIPK1-driven apoptosis and inflammation
a Hematoxylin and eosin (HE) staining and immunohistochemistry (IHC) of CD45 of liver sections from 8-month-old mice of indicated genotypes. Representative images out of n = 8 (Senp1f/f), n = 6 (Senp1f/f;Alb-Cre and Senp1f/f;Alb-Cre;Ripk1D138N/D138N) mice are represented. Arrows indicate infiltration of macrophages. Graph depicting numbers of CD45+ foci on liver sections of indicated genotypes. b Volcano plots showing fold-change and P-value for the comparison of 3-month-old Senp1f/f;Alb-Cre livers versus Senp1f/f livers (n = 3). Differentially expressed genes (fold change >1.5, P value < 0.05) are depicted in red (upregulated) and blue (downregulated). Representative genes associated with inflammatory response (TNFα signaling, black) and fibrosis (collagen, yellow) are highlighted. c, Quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis of the mRNA expression of cytokines and chemokines from livers of 8-month-old mice of indicated genotypes (n = 8 for Senp1f/f, n = 6 for Senp1f/f;Alb-Cre and Senp1f/f;Alb-Cre;Ripk1D138N/D138N). d Oil Red O staining of lipids in liver sections from 8-month-old mice of indicated genotypes. Representative images out of n = 8 (Senp1f/f), n = 6 (Senp1f/f;Alb-Cre and Senp1f/f;Alb-Cre;Ripk1D138N/D138N) mice are represented. Graph depicting percentage of lipid content on liver sections of indicated genotypes. e Triglyceride (TG) and total cholesterol (TC) concentrations in the livers of mice from the indicated groups (n = 5). f Representative images of Masson’s trichrome stained (MTS) liver sections from 8-month-old mice of indicated genotypes. Representative images out of n = 8 (Senp1f/f), n = 6 (Senp1f/f;Alb-Cre and Senp1f/f;Alb-Cre;Ripk1D138N/D138N) mice are represented. Graph depicting percentage of fibrosis area on liver sections of indicated genotypes. g Quantitative RT-PCR analysis of the mRNA expression of fibrogenic parameters from livers of 8-month-old mice of indicated genotypes (n = 8 for Senp1f/f, n = 6 for Senp1f/f;Alb-Cre and Senp1f/f;Alb-Cre;Ripk1D138N/D138N). h Immunohistochemistry of hepatic stellate cells (HSC) marker Desmin in the livers of indicated genotypes. Representative images out of n = 5 mice for each genotype are represented. Data are expressed as mean ± s.e.m. (a, c–h). One-way ANOVA, post hoc Dunnett’s test (a, c–h). Source data are provided as a Source Data file.
