Administration of exogenous uPA to uPA^−/− mice. uPA^−/− mice were subjected to cardiotoxin muscle injury and either left untreated (No treat) or treated with intramuscular injection of exogenous uPA daily from 1 to 4 days after injury (uPA inject), and muscles collected at 5 days after injury. (Top) Muscle homogenates subjected to heparin sulfate affinity purification and then Western blotting for HGF. Note that treatment with exogenous uPA rescued HGF levels in muscle of uPA^−/− mice. (Middle) Muscle cryosections stained with hematoxylin and eosin for morphologic analysis. Note the restoration of muscle regeneration in uPA^−/− mice after treatment with uPA. Scale bar represents 50 μm. (Bottom) Quantitative analysis of morphology. WT indicates wild-type no treatment; WT-I, wild-type injected with uPA; uPA^−/−, uPA^−/− no treatment; and uPA^−/−I, uPA^−/− injected with uPA. Regenerating fibers identified as central nucleated fibers and counted in 2 sections per muscle and expressed as number per square millimeter muscle area. Damaged area estimated by subtracting summed area of normal and regenerating fibers from total muscle area. Bars represent mean ± SE; n = 4 to 6 per group. *Mean value significantly different from that for WT mice (P < .05).