| First Author | Koh TJ | Year | 2005 |
| Journal | Am J Physiol Cell Physiol | Volume | 289 |
| Issue | 1 | Pages | C217-23 |
| PubMed ID | 15716324 | Mgi Jnum | J:104684 |
| Mgi Id | MGI:3612627 | Doi | 10.1152/ajpcell.00555.2004 |
| Citation | Koh TJ, et al. (2005) Mice deficient in plasminogen activator inhibitor-1 have improved skeletal muscle regeneration. Am J Physiol Cell Physiol 289(1):C217-23 |
| abstractText | 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-/- 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-/-, and PAI-1-deficient (PAI-1-/-) mice. As expected, there was no uPA activity in the injured muscles of uPA-/- mice, and muscles from these transgenic animals demonstrated impaired regeneration. On the other hand, uPA activity was increased in injured muscle from PAI-1-/- mice to a greater extent than in wild-type controls. Furthermore, PAI-1-/- 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. |
