The urokinase-type plasminogen activator receptor is not required for skeletal muscle inflammation or regeneration.
The hypothesis of this study was the urokinase-type plasminogen activator receptor (uPAR) is required for accumulation of inflammatory cells in injured skeletal muscle and for efficient muscle regeneration. Expression of uPAR was elevated at 1 and 3 days after cardiotoxin-induced muscle injury in wild-type mice before returning to baseline levels. Neutrophil accumulation peaked 1 day postinjury in muscle from both wild-type (WT) and uPAR null mice, while macrophage accumulation peaked between 3 and 5 days postinjury, with no differences between strains. Histological analyses confirmed efficient muscle regeneration in both wild-type and uPAR null mice, with no difference between strains in the formation or growth of regenerating fibers, or recovery of normal morphology. Furthermore, in vitro experiments demonstrated that chemotaxis is not different between WT and uPAR null macrophages. Finally, fusion of cultured satellite cells into multinucleated myotubes was not different between cells isolated from WT and uPAR null mice. These results demonstrate that uPAR is not required for the accumulation of inflammatory cells or the regeneration of skeletal muscle following injury, suggesting uPA can act independently of uPAR to regulate events critical for muscle regeneration.
Bryer
Scott C
SC
Department of Movement Sciences, University of Illinois at Chicago, 1919 W. Taylor Street, Chicago, Il 60612, USA.
Koh
Timothy J
TJ
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002459:Cell Fusion; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D004179:Cobra Cardiotoxin Proteins; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000473:pathology; D009220:Myositis / Q000139:chemically induced / Q000503:physiopathology*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D012038:Regeneration / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D032496:Satellite Cells, Skeletal Muscle / Q000187:drug effects / Q000502:physiology
D019138:Antibodies, Blocking; D004179:Cobra Cardiotoxin Proteins; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator