TY - JOUR
T1 - Urokinase-dependent plasminogen activation is required for efficient skeletal muscle regeneration in vivo
AU - Lluis, F
AU - Roma, J
AU - Suelves, M
AU - Parra, M
AU - Aniorte, G
AU - Gallardo, E
AU - Illa, I
AU - Rodriguez, L
AU - Hughes, S M
AU - Carmeliet, P
AU - Roig, M
AU - Munoz-Canoves, P
PY - 2001/3/15
Y1 - 2001/3/15
N2 - Plasminogen activators urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) are extracellular proteases involved in various tissue remodeling processes. A requirement for uPA activity in skeletal myogenesis was recently demonstrated in vitro. The role of plasminogen activators in skeletal muscle regeneration in vivo in wild-type, uPA-deficient, and tPA-deficient mice is investigated here. Wild-type and tPA-/- mice completely repaired experimentally damaged skeletal muscle. In contrast, uPA-/- mice had a severe regeneration defect, with decreased recruitment of blood-derived monocytes to the site of injury and with persistent myotube degeneration. in addition, uPA-deficient mice accumulated fibrin in the degenerating muscle fibers; however, the defibrinogenation of uPA-deficient mice resulted in a correction of the muscle regeneration defect. A similar severe regeneration deficit with persistent fibrin deposition was also reproducible in plasminogen-deficient mice after injury, suggesting that fibrinolysis by uPA-mediated plasminogen activation plays a fundamental role in skeletal muscle regeneration. In conclusion, the uPA-plasmin system is identified as a critical component of the mammalian skeletal muscle regeneration process, possibly because it prevents intramuscular fibrin accumulation and contributes to the adequate inflammatory response after injury. These studies demonstrate the requirement of an extracellular proteolytic cascade during muscle regeneration in vivo.(Blood. 2001;97:1703-1711) (C) 2001 by The American Society of Hematology.
AB - Plasminogen activators urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) are extracellular proteases involved in various tissue remodeling processes. A requirement for uPA activity in skeletal myogenesis was recently demonstrated in vitro. The role of plasminogen activators in skeletal muscle regeneration in vivo in wild-type, uPA-deficient, and tPA-deficient mice is investigated here. Wild-type and tPA-/- mice completely repaired experimentally damaged skeletal muscle. In contrast, uPA-/- mice had a severe regeneration defect, with decreased recruitment of blood-derived monocytes to the site of injury and with persistent myotube degeneration. in addition, uPA-deficient mice accumulated fibrin in the degenerating muscle fibers; however, the defibrinogenation of uPA-deficient mice resulted in a correction of the muscle regeneration defect. A similar severe regeneration deficit with persistent fibrin deposition was also reproducible in plasminogen-deficient mice after injury, suggesting that fibrinolysis by uPA-mediated plasminogen activation plays a fundamental role in skeletal muscle regeneration. In conclusion, the uPA-plasmin system is identified as a critical component of the mammalian skeletal muscle regeneration process, possibly because it prevents intramuscular fibrin accumulation and contributes to the adequate inflammatory response after injury. These studies demonstrate the requirement of an extracellular proteolytic cascade during muscle regeneration in vivo.(Blood. 2001;97:1703-1711) (C) 2001 by The American Society of Hematology.
UR - http://www.scopus.com/inward/record.url?scp=0035869496&partnerID=8YFLogxK
U2 - 10.1182/blood.V97.6.1703
DO - 10.1182/blood.V97.6.1703
M3 - Article
SN - 1528-0020
VL - 97
SP - 1703
EP - 1711
JO - Blood
JF - Blood
IS - 6
ER -