Liver regeneration is transiently impaired in urokinase-deficient mice

To test the hypothesis that urokinase-type plasminogen activator (uPA) play s an important role in liver regeneration in vivo, partial hepatectomy was performed on wild-type and uPA-deficient (uPA-/-) mice. Mice were studied a t 24, 44, and 96 h and at 8 days and 4 wk post-partial hepatectomy for evid ence of regeneration, as measured by mitotic indexes and [H-3]thymidine inc orporation. In wild-type mice, thymidine incorporation peaked at 44 h and t his index was reduced by 47% in uPA-/- mice (P = 0.02). By 8 days, however, liver mass was comparable in both groups. Histological analysis revealed t he presence of focal areas of fibrin deposition and cellular loss by 24 h t hat were more severe and prevalent in uPA-/- mice than in wild-type mice (6 2 and 23%, respectively; chi(2) = 3.939, P = 0.047). In contrast, regenerat ion was not impaired in uPA receptor (uPAR)-deficient mice at 24 and 44 h. Taken together, these data indicate that uPA, independent of its interactio n with the uPAR, plays an important role in liver regeneration in vivo.