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Adenosine A3 Receptor Agonists (A3RA) Induce Favorable Alterations in the MMP/TIMP Response in Skeletal Muscle Following Traumatic Injury
Author(s) -
Urso Maria Laina,
Wang Ruibo,
Zambraski Edward J,
Liang Bruce T
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.600.2
Subject(s) - skeletal muscle , endocrinology , medicine , matrix metalloproteinase , downregulation and upregulation , adenosine , chemistry , receptor , biochemistry , gene
Our prior work identified robust changes in the expression of the Matrix Metalloproteases (MMPs) & their inhibitors (TIMPs) 3–72 h post‐injury in skeletal muscle. Dramatic upregulation of the MMPs is hypothesized to interfere with proper skeletal muscle regeneration. Because adenosine can provide protection in cardiac muscle, we evaluated the effects of an A3RA (CI‐IB‐MECA), on MMP & TIMP expression in skeletal muscle. Sixty mice were injected with Evans blue dye (EBD) & the A3RA, or a placebo (P) 2 h pre‐injury. Injury was induced by applying a cold (−20C) steel probe to the tibialis anterior (TA). TA samples were collected from injured & contralateral legs 3, 10, 24, 48, & 72 h post‐injury. qRT‐PCR was used to quantify mRNA. EBD analysis 24 h post‐injury indicated a trend (p=0.06) towards reduced percentage of injured cells in A3RA‐treated mice versus P‐treated (42% vs. 57%). A3RA‐treatment significantly (p<0.05) modulated the response of MMP‐2 (A3RA: no change (NC) vs. P: 9‐fold decrease); MMP‐3 (A3RA: 13‐fold vs. P: 17‐fold increase); MMP‐9 (A3RA: 2‐fold vs. P: 23‐fold increase); MT1‐MMP (A3RA: NC vs. P: 25‐fold decrease); TIMP‐1 (A3RA: 4‐fold vs. P: 27‐fold increase); & TIMP‐2 (A3RA: 2‐fold increase vs. P: 6‐fold decrease). These data suggest that the A3R is a novel target for ameliorating skeletal muscle injury through favorable alterations in the MMP/TIMP response.