title: Macrophage-specific expression of urokinase-type plasminogen activator promotes skeletal muscle regeneration.
abstract: Macrophages (Mp) and the plasminogen system play important roles in tissue repair following injury. We hypothesized that Mp-specific expression of urokinase-type plasminogen activator (uPA) is sufficient for Mp to migrate into damaged muscle and for efficient muscle regeneration. We generated transgenic mice expressing uPA only in Mp, and we assessed the ability of these mice to repair muscle injury. Mp-only uPA expression was sufficient to induce wild-type levels of Mp accumulation, angiogenesis, and new muscle fiber formation. In mice with wild-type uPA expression, Mp-specific overexpression further increased Mp accumulation and enhanced muscle fiber regeneration. Furthermore, Mp expression of uPA regulated the level of active hepatocyte growth factor, which is required for muscle fiber regeneration, in damaged muscle. In vitro studies demonstrated that uPA promotes Mp migration through proteolytic and nonproteolytic mechanisms, including proteolytic activation of hepatocyte growth factor. In summary, Mp-derived uPA promotes muscle regeneration by inducing Mp migration, angiogenesis, and myogenesis.
authors.affiliation: Department of Kinesiology and Nutrition, University of Illinois, Chicago, IL 60612, USA.
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Novak
authors.forename: Scott C
authors.initials: SC
authors.lastname: Bryer
authors.forename: Ming
authors.initials: M
authors.lastname: Cheng
authors.forename: Mai-Huong
authors.initials: MH
authors.lastname: Nguyen
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Conley
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Cunningham
authors.forename: Bing
authors.initials: B
authors.lastname: Xue
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Sisson
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: You
authors.forename: Troy A
authors.initials: TA
authors.lastname: Hornberger
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Koh
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D024510:Muscle Development / Q000235:genetics / Q000276:immunology; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000276:immunology; D012038:Regeneration / Q000235:genetics / Q000276:immunology*; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics*
chemical_list: D014568:Urokinase-Type Plasminogen Activator