title: Mice deficient in urokinase-type plasminogen activator have delayed healing of tympanic membrane perforations.
abstract: Mice deficient in plasminogen, the precursor of plasmin, show completely arrested healing of tympanic membrane (TM) perforations, indicating that plasmin plays an essential role in TM healing. The activation of plasminogen to plasmin is performed by two plasminogen activators (PAs), urokinase-type PA (uPA) and tissue-type PA (tPA). To elucidate the functional roles of PAs in the healing of TM perforations, we investigated the phenotypes of single gene-deficient mice lacking uPA (uPA(-/-)) or tPA (tPA(-/-)) after TM perforation. Delayed healing of TM perforations was observed in uPA(-/-) mice but not tPA(-/-) mice. The migration of keratinocytes was clearly delayed and seemed to be misoriented in uPA(-/-) mice. Furthermore, fibrin deposition and the inflammatory response were persistent in these mice. Our findings demonstrate that uPA plays a role in the healing of TM perforations. The observed phenotypes in uPA(-/-) mice are most likely due to the reduced generation of plasmin.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
authors.forename: Yue
authors.initials: Y
authors.lastname: Shen
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Guo
authors.forename: Chun
authors.initials: C
authors.lastname: Du
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Wilczynska
authors.forename: Sten
authors.initials: S
authors.lastname: Hellström
authors.forename: Tor
authors.initials: T
authors.lastname: Ny
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D005341:Fibrinolysin / Q000096:biosynthesis; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000502:physiology; D007633:Keratins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D038781:Otoscopy; D010641:Phenotype; D010959:Tissue Plasminogen Activator / Q000172:deficiency / Q000235:genetics; D018058:Tympanic Membrane Perforation / Q000503:physiopathology*; D014568:Urokinase-Type Plasminogen Activator / Q000172:deficiency* / Q000235:genetics; D014945:Wound Healing / Q000502:physiology*
chemical_list: D007633:Keratins; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator