{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:53:49Z","timestamp":1790132029119,"version":"4.0.1"},"reference-count":59,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2012,2,15]]},"abstract":"<jats:p>We have previously demonstrated that in response to traumatic injury in skeletal muscle, there is a dysregulation of the matrix metalloproteases (MMPs) and their inhibitors (TIMPs), a response hypothesized to interfere with proper skeletal muscle regeneration. Moreover, we have shown that pharmacological activation of the adenosine A<jats:sub>3<\/jats:sub>receptor by Cl-IBMECA in skeletal muscle can protect against ischemia-reperfusion and eccentric exercise injury. However, the mechanism by which Cl-IBMECA protects muscle tissue is poorly defined. This study evaluated the effects of Cl-IBMECA on MMP\/TIMP expression in skeletal muscle and tested the hypothesis that adenosine A<jats:sub>3<\/jats:sub>receptor-stimulated protection of skeletal muscle following traumatic injury is associated with a blunting of MMPs involved in inflammatory processes and collagen degradation, and an increase in MMPs associated with extracellular matrix remodeling. Sixty C57BL\/6J male mice were injected with Cl-IBMECA ( n = 30) or a vehicle ( n = 30), and Evans blue dye. Injury was induced by applying a cold steel probe (\u221279\u00b0C) to the tibialis anterior (TA) muscle for 10 s. TA muscles from uninjured and injured legs were collected 3, 10, and 24 h postinjury for analysis of muscle injury and MMP\/TIMP mRNA and protein levels. Twenty-four hours postinjury, 56.8% of the fibers were damaged in vehicle-treated mice vs. 35.4% in Cl-IBMECA-treated mice ( P = 0.02). Cl-IBMECA treatment reduced membrane type 1 (MT1)-MMP, MMP-3, MMP-9, and TIMP-1 mRNA expression 2- to 20-fold compared with vehicle-treated mice ( P &lt; 0.05). Cl-IBMECA decreased protein levels of latent\/shed MT1-MMP 23\u20132,000%, respectively, 3\u201310 h postinjury. In Cl-IBMECA-treated mice, latent MMP-2 was decreased 20% 3 h postinjury, active MMP-3 was decreased 64% 3 h postinjury, and latent\/active MMP-9 was decreased 417,631% 3 h postinjury and 20% 10 h postinjury. Protein levels of active MMP-2 and latent MMP-3 were increased 25% and 74% 3 h postinjury, respectively. The present study elucidates a new protective role of adenosine A<jats:sub>3<\/jats:sub>receptor stimulation in posttraumatic skeletal muscle injury.<\/jats:p>","DOI":"10.1152\/japplphysiol.00809.2011","type":"journal-article","created":{"date-parts":[[2011,11,24]],"date-time":"2011-11-24T05:51:59Z","timestamp":1322113919000},"page":"658-670","source":"Crossref","is-referenced-by-count":15,"title":["Adenosine A<sub>3<\/sub>receptor stimulation reduces muscle injury following physical trauma and is associated with alterations in the MMP\/TIMP response"],"prefix":"10.1152","volume":"112","author":[{"given":"Maria L.","family":"Urso","sequence":"first","affiliation":[{"name":"U.S. Army Research Institute of Environmental Medicine, Military Performance Division, Natick, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruibo","family":"Wang","sequence":"additional","affiliation":[{"name":"Pat and Jim Calhoun Cardiology Center, University of Connecticut 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