Partial hepatectomy triggers hepatic accumulation of Fn14(+) cells in WT mice.

<p>Healthy adult wild type (WT) mice (n = 80) underwent PH. Expression of Fn14 was evaluated at various time points by (A) qRT-PCR analysis, (B) Representative western blot, quantification of protein levels for Fn14 normalized to β-actin and (C) Immunohistochemistry (magnification 20×). To assure reagent specificity, similar analysis was done in mice that were genetically-deficient in Fn14(Fn14 KO). Mean +/− SEM results from all mice (n = 4–5/time point) are graphed relative to baseline, pre-PH (time 0), * p<0.05.</p

Deletion of Fn14 inhibits post- PH proliferation of hepatocytes and cholangiocytes.

<p>Fn14 KO mice and wild type (WT) mice underwent PH. Proliferative activity was evaluated by (A) BrdU incorporation and (B) Ki67 immunostaining. Representative images are displayed (magnification 20×). Arrows indicate Brdu(+) or Ki67(+) cells (red-hepatocyte, black-ductular cells). Labeled hepatocytes/ductular cells were counted in 10 randomly-selected 20× magnification fields/section. Mean +/− SEM results from all mice (n = 3–4/group/time point) are graphed relative to baseline, pre-PH (time 0) in WT group. * p<0.05 vs time 0, # p<0.05 vs WT. Representative images of 48 hours post-PH liver are displayed (magnification 20×).</p

Deletion of Fn14 impairs liver regeneration and survival after PH.

<p>Healthy adult wild type (WT) and Fn14 KO mice underwent PH. (A) Liver regeneration ratios (assessed by dividing liver weight at sacrifice by the estimated original liver weight) were compared between WT and Fn14 KO mice at various time points post-PH. (B) Serum bilirubin levels were measured using a Total Bilirubin Test Kit (BIOTRON Diagnostics). (C) Percentage of infarct areas per high-powered field (HPF) were also quantified at in 50 randomly-chosen fields/section. Mean +/− SEM results from 3–4 mice/group/time point are shown. * p<0.01 vs WT. (D) Survival rates were compared between WT and Fn14 KO mice at various time points post-PH. The P values for survival curve are calculated using the log rank test.</p

TWEAK is required for optimal liver regeneration after PH.

<p>TWEAK KO mice, WT mice and WT mice that were treated with anti-TWEAK antibodies underwent PH. Expression of progenitor markers was evaluated at various time points by (A) qRT-PCR analysis and (B) Immunohistochemistry. Mean +/− SEM results from all mice (n = 5/time point) are graphed relative to baseline, pre-PH (time 0) in WT group, * p<0.05 vs time 0, # p<0.05 vs WT. Representative images of 48 hours post-PH liver are displayed (magnification 20×).</p