Fig. 7: Activation of noncanonical NF-κB induces CXCL13 expression in macrophages to inhibit liver regeneration.

A Relative levels of CXCL13 mRNA transcripts in immune cells and nonimmune cells isolated from mouse livers after 2/3 PHx at 0 h and 6 h (PHx at 0 h, n = 4; PHx at 6 h, n = 5). Statistical significance was made with the Student’s t test. B Diagram of the experimental model of chimeric bone marrow mice with 2/3 PHx. C Liver/body weight ratios in chimeric mice at 36 h and 48 h (n = 6). Statistical significance was made with the ANOVA test. D, E Representative immunofluorescence images of liver Ki67⁺HNF4α⁺ cells in chimeric mice at 36 h and quantification of the percentage of Ki67⁺HNF4α⁺ cells (n = 6). Statistical significance was made with the ANOVA test. F Western blot analysis of PCNA and Cyclin D1 expression levels in the livers of chimeric mice after 2/3 PHx, and the band intensity was quantified by densitometry (n = 6). Statistical significance was made with the ANOVA test. G Representative immunofluorescence images of CXCL13 (green) and F4/80 (red) in mouse livers after 2/3 PHx. H Relative levels of CXCL13 mRNA transcripts in hepatic macrophages after 2/3 PHx (n = 6). Statistical significance was made with the Student’s t test. I Western blot analysis of NF-κB2 expression in hepatic macrophages after 2/3 PHx, and the band intensity was quantified by densitometry (n = 6). Statistical significance was made with the Student’s t test. J BMDMs transfected with NC siRNA or NIK siRNA were stimulated with LTα1β2 for 24 h, and the relative levels of CXCL13 mRNA were detected (n = 3). Statistical significance was made with the ANOVA test. K BMDMs were pretreated with or without PS1145 and then stimulated with LTα1β2 for 24 h, the relative levels of CXCL13 mRNA were detected (n = 3). Statistical significance was made with the ANOVA test. L Diagram of the experimental model of PS1145 administration in mice subjected to 2/3 PHx. M Relative levels of CXCL13 mRNA at 24 h in livers from mice treated with or without PS1145 after 2/3 PHx (n = 6). Statistical significance was made with the Student’s t test. N Liver/body weight ratios were determined in mice treated with or without PS1145 after 2/3 PHx (n = 6). Statistical significance was made with the Student’s t test. O, P Representative immunofluorescence costaining images of Ki67⁺HNF4α⁺ liver cells in the indicated mice at 36 h after 2/3 PHx and quantification of the percentage of Ki67⁺HNF4α⁺ cells (n = 6). Statistical significance was made with the Student’s t test. Q Western blot analysis of PCNA and Cyclin D1 expression levels in liver tissues from mice treated with or without PS1145 at 36 h after 2/3 PHx, and the band intensity was quantified by densitometry (n = 6). Statistical significance was made with the Student’s t test.