Effect of systemic fibrinogen depletion on muscle regeneration of uPA-deficient mice.

uPA-deficient mice were implanted 3 days before glycerol-induced muscle degeneration with ancrod-filled mini-osmotic pumps (3 U/d over 12 days) (Ancrod) or with buffered-filled pumps (Saline). (A) Ancrod treatment reduces fibrinogen in blood of uPA-deficient mice. Forty micrograms sodium citrate–treated blood obtained from saline- or ancrod-infused mice was analyzed in a 6% polyacrylamide gel by Western blotting using a polyclonal antimouse fibrinogen antibody (1:1000). The 340-kd approximate molecular mass species corresponds to murine fibrinogen and was calculated according to standard molecular mass markers electrophoresed in an adjacent lane. (B) Fibrinogen depletion restores muscle regeneration in uPA-deficient mice. Cryosections from saline- and ancrod-treated uPA-deficient mice were stained with H&E 9 days after injury. Although well-advanced regeneration is visible in ancrod-treated uPA−/− mice, a regeneration defect is still observed in saline-treated mice 9 days after injury.