Lacerated muscles of PAI-1–deficient mice have an exacerbated fibrogenesis with increased TGF-β1 activation, miR-21 expression, and collagen deposition. (A) Muscle injury was performed by laceration in the TA muscles of WT mice as well as in PAI-1^−/−, uPA^−/−, and uPA^+/− mice. A representative example of Sirius red staining of muscle sections at 21 d after laceration of the distinct genotypes is shown. Bar, 25 µm. (B) The extent of collagen deposition was quantified in lacerated muscles of all mouse genotypes (*, P < 0.01; means ± SEM; n = 5 for each group). (C) Analysis of miR-21 expression by quantitative PCR in muscles of mice of the indicated genotypes (*, P < 0.05; **, P < 001; means ± SEM; n = 4 for each group). (D) Active TGF-β1 protein quantification by ELISA in muscles of the same genotypes (*, P < 0.05; means ± SEM; n = 6 for each group). (E) Extracts of PAI-1^−/− and uPA^−/−-lacerated muscles were analyzed by Western blotting for P-Smad2, total Smad2/3 protein, and β-actin. Quantification of P-Smad2 versus total Smad2/3 and normalized for β-actin levels is shown (*, P < 0.05; **, P < 0.01; means ± SEM; n = 7 for each group).