{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:28:35Z","timestamp":1791246515026,"version":"4.1.0"},"reference-count":44,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2005,7]]},"abstract":"<jats:p> Skeletal muscle possesses a remarkable capacity for regeneration. Although the regulation of this process at the molecular level remains largely undefined, the plasminogen system appears to play a critical role. Specifically, mice deficient in either urokinase-type plasminogen activator (uPA<jats:sup>\u2212\/\u2212<\/jats:sup> mice) or plasminogen demonstrate markedly impaired muscle regeneration after injury. In the present study, we tested the hypothesis that loss of the primary inhibitor of uPA, plasminogen activator inhibitor-1 (PAI-1), would improve muscle regeneration. Repair of the extensor digitorum longus muscle was assessed after cardiotoxin injury in wild-type, uPA<jats:sup>\u2212\/\u2212<\/jats:sup>, and PAI-1-deficient (PAI-1<jats:sup>\u2212\/\u2212<\/jats:sup>) mice. As expected, there was no uPA activity in the injured muscles of uPA<jats:sup>\u2212\/\u2212<\/jats:sup> mice, and muscles from these transgenic animals demonstrated impaired regeneration. On the other hand, uPA activity was increased in injured muscle from PAI-1<jats:sup>\u2212\/\u2212<\/jats:sup> mice to a greater extent than in wild-type controls. Furthermore, PAI-1<jats:sup>\u2212\/\u2212<\/jats:sup> mice demonstrated increased expression of MyoD and developmental myosin after injury as well as accelerated recovery of muscle morphology, protein levels, and muscle force compared with wild-type animals. The injured muscles of PAI-1-null mice also demonstrated increased macrophage accumulation, contrasting with impaired macrophage accumulation in uPA-deficient mice. The extent of macrophage accumulation correlated with both the clearance of protein after injury and the efficiency of regeneration. Taken together, these results indicate that PAI-1 deficiency promotes muscle regeneration, and this protease inhibitor represents a therapeutic target for enhancing muscle regeneration. <\/jats:p>","DOI":"10.1152\/ajpcell.00555.2004","type":"journal-article","created":{"date-parts":[[2005,2,17]],"date-time":"2005-02-17T01:23:53Z","timestamp":1108603433000},"page":"C217-C223","source":"Crossref","is-referenced-by-count":62,"title":["Mice deficient in plasminogen activator inhibitor-1 have improved skeletal muscle regeneration"],"prefix":"10.1152","volume":"289","author":[{"given":"Timothy J.","family":"Koh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott C.","family":"Bryer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augustina M.","family":"Pucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Sisson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Abraham E, Gyetko MR, Kuhn K, Arcaroli J, Strassheim D, Park JS, Shetty S, and Idell S. 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