TG2 deficiency enhances FXIII-directed Fibγ-Fibγ cross-linking in the APAP-injured liver. Male wild-type mice, FXIII-A^−/− mice, or TG2^−/− mice were challenged with 300 mg/kg APAP or vehicle (sterile saline), and liver samples were collected 24 hours later. Hepatic Fibα cross-linking was measured in enriched insoluble liver extracts using capillary western blotting. Representative digital capillary renderings are shown depicting increased hepatic levels of HMW (>300 kDa) cross-linked Fibα (HMW Fibα) in livers of APAP-challenged mice (A) and impact of TG2 deficiency on hepatic levels of HMW Fibα in livers of APAP-challenged mice (B). (C) Quantification of HMW Fibα in livers of APAP-challenged wild-type and FXIII-A^−/− mice and (D) HMW Fibα levels expressed relative to total insoluble fibrin(ogen) (detected as insoluble Fibβ). (E) Quantification of HMW Fibα levels in livers of APAP-challenged wild-type and TG2^−/− mice and (F) HMW Fibα levels expressed relative to total insoluble fibrin(ogen) (detected as insoluble Fibβ). Results from individual mice are plotted and bars represent mean ± SEM. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001.