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Research article2012Peer reviewedOpen access

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

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

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.

Published in

PLoS ONE
2012, Volume: 7, number: 12, article number: e51303

    UKÄ Subject classification

    Physiology

    Publication identifier

    DOI: https://doi.org/10.1371/journal.pone.0051303

    Permanent link to this page (URI)

    https://res.slu.se/id/publ/85848