TG2 inhibits 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 Fibγ cross-linking was measured in enriched insoluble liver extracts using capillary western blotting. Representative digital capillary renderings are shown depicting increased hepatic levels of Fibγ-Fibγ dimer in livers of APAP-challenged mice (A) and impact of TG2 deficiency on hepatic levels of Fibγ-Fibγ dimer in livers of APAP-challenged mice (B). (C) Quantification of Fibγ-Fibγ dimer in livers of APAP-challenged wild-type and FXIII-A^−/− mice. (D) Quantification of Fibγ-Fibγ dimer in livers of APAP-challenged wild-type and TG2^−/− mice. (E) Fibγ-Fibγ dimer 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. ND, not detected.