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Mice Deficient in Urokinase-Type Plasminogen Activator Have Delayed Healing of Tympanic Membrane Perforations

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Title
Mice Deficient in Urokinase-Type Plasminogen Activator Have Delayed Healing of Tympanic Membrane Perforations
Published in
PLOS ONE, December 2012
DOI 10.1371/journal.pone.0051303
Pubmed ID
Authors

Yue Shen, Yongzhi Guo, Chun Du, Malgorzata Wilczynska, Sten Hellström, Tor Ny

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.

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Geographical breakdown

Country Count As %
Unknown 12 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 4 33%
Lecturer 2 17%
Professor 1 8%
Other 1 8%
Student > Ph. D. Student 1 8%
Other 1 8%
Unknown 2 17%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 5 42%
Medicine and Dentistry 2 17%
Agricultural and Biological Sciences 1 8%
Pharmacology, Toxicology and Pharmaceutical Science 1 8%
Unknown 3 25%