Fig. 7: Loss of A1AT blunts the IL-32γ-mediated protective action via proteolytic degradation and cleavage.
From: A1AT dysregulation of metabolically stressed hepatocytes by Kupffer cells drives MASH and fibrosis
a, Immunoblot analysis of serum A1AT obtained from the NCD- and FFD-fed hIL-32γ Tg mice and the NCD- and FFD-fed Tg/A1AT KO mice. b, Serum PR3 concentration of each group measured via ELISA. NCD-fed Tg mice, n = 5; NCD-fed Tg/KO mice, n = 5; FFD-fed Tg mice, n = 8 and FFD-fed Tg/KO mice, n = 8 were used. c, Hepatic expression of the IL-32γ protein in the NCD- and FFD-fed hIL-32γ Tg mice and the NCD- and FFD-fed hIL-32γ Tg/A1AT KO mice. d, Immunoblot analysis of serum IL-32γ in the NCD- and FFD-fed hIL-32γ Tg mice and FFD-fed hIL-32γ Tg/A1AT KO mice. e, Serum IL-32γ concentrations in each group were measured via ELISA. f, Correlation between the serum level of PR3 and that of IL-32γ in hIL-32γ Tg and hIL-32γ Tg/A1AT KO mice. g, Graphical abstract showing PR3-mediated IL-32γ degradation and cleavage in A1AT-depleted conditions. h–j, BWs (h), LWs (i) and LBW ratios (j) in each group. k, Images of freshly collected livers and liver sections from each representative group stained with H&E and BODIPY. l, IHC staining image of CLEC4F-positive KCs in FFD-fed Tg mice and FFD-fed Tg/KO mice. m, Correlation between the serum levels of IL-32γ and ALT in Tg and Tg/KO mice. n,o, Relative mRNA expression of proinflammatory genes (n) and profibrogenic genes (o) in hepatic tissue samples from each group. p, Representative images of Sirius red-stained liver sections from each group. Each representative image of a whole-body liver section was analyzed for the Sirius red-positive area. q, Detection of cleaved IL-32γ in serum samples from the control group (CRTL.) and in patients with MASLD via western blotting (n = 12). r, Serum IL-32γ levels in the control group and in patients with MASLD were measured via ELISA. s, Correlations between the serum levels of IL-32γ, ALT and AST in the control group and in patients with MASLD. The data are presented as the means ± s.d.; *,#P < 0.05, **,##P < 0.01, ***,###P < 0.001 and ****,####P < 0.0001 versus the control model. ns, not significant.
