Figure 1.
DACH1 deletion in hepatocytes increases liver tPA, plasma tPA and systemic fibrinolytic activity in mice. (A) Experimental scheme for depleting hepatocyte DACH1 in adult mice and immunoblot of liver DACH1 in these mice, with β-actin as loading control. Dach1fl/fl mice were injected IV with AAV8-TBG-Cre (Cre) to create HC-DACH1–KO mice, with AAV8-TBG-LacZ–injected Dach1fl/fl mice (LacZ) serving as controls. (B) Plat mRNA in liver normalized to Rplp0 and expressed as relative to the value in LacZ mice. (C) Plasma tPA concentration by ELISA. (D) Plasma tPA activity by enzymatic assay. (E) Plasma PAI-1–free tPA concentration by ELISA. (F) Plasma fibrinogen-fibrin antigen concentration by ELISA. (G) Plasma clottable fibrinogen concentration by Clauss fibrinogen assay. The data are expressed relative to the value in plasma of LacZ mice. The absolute values using human fibrinogen for the standard curve were 2.27 ± 0.14 (LacZ) and 1.43 ± 0.14 (Cre) mg/mL. (H) Concentration of fibrin degradation products in plasma by ELISA. (I) Fibrinolytic activity measured by euglobulin clot lysis assay from plasma. Horizontal lines in dot-density plots indicate mean values. n = 8 to 10 mice per group (A-H); 4 mice per group (I). *P < .05, **P < .01, ***P < .001, Mann-Whitney U test (B), Student t test (C-F,I).