Fig. 7: Khsrp protects against ALF partially by regulating pre-mRNA splicing.

A Scatter plots show changes in splicing events between Ctrl and CCl4-treated groups. Using rMATS, five types of AS events were analyzed: Retained introns (RIs), skipped exons, alternative 5′and 3′splice sites (A5SS and A3SS, respectively), and mutually exclusive exons. Significantly changed events (|ΔPSI| > 0.05, FDR < 0.05, and supporting reads ≥ 5) are shown by color dots. B Volcano plots showing up- or downregulated exons and introns in control or CCl4-treated groups according to RNA-Seq analysis. C Schematic diagram of the experimental setup. Mice (n = 6) were first injected with Khsrp vectors or controls for 4 h via hydrodynamic tail-vein injections, after which they were intraperitoneally injected with CCl4 and/or PB for an additional 24 h. D Protein levels of KHSRP, EGFR, SF3B1, PHF5A, and SSR4 in mouse livers treated with CCl4 for 24 h in the presence or absence of PB according to Western blotting. Graph shows protein levels as means ± SEM. E H&E staining of liver sections from Khsrp-overexpressing mice treated with CCl4 in the presence or absence of PB (scale bar: 100 μm). Necrosis quantification is shown in the below panel. Expression of KHSRP, SF3B1, PHF5A, and KI67 proteins was detected using immunohistochemistry (scale bar: 50 μm). Immunohistochemistry analysis and quantification of a TUNEL assay (red) in the liver sections (scale bar: 100 μm). F Plasma ALT and AST levels in mice. *p < 0.05.