PMID- 20349081 OWN - NLM STAT- MEDLINE DCOM- 20101007 LR - 20211020 IS - 1439-6327 (Electronic) IS - 1439-6319 (Linking) VI - 109 IP - 5 DP - 2010 Jul TI - Matrix metalloprotease-3 and tissue inhibitor of metalloprotease-1 mRNA and protein levels are altered in response to traumatic skeletal muscle injury. PG - 963-72 LID - 10.1007/s00421-010-1435-5 [doi] AB - The purpose of this study was to characterize the time course of matrix metalloprotease-3 (MMP-3) and tissue inhibitor of metalloprotease-1 (TIMP-1) expression in mouse tibialis anterior (TA) muscle post-injury. Mice were anesthetized, the TA muscle exposed, and injury induced by applying a cold steel probe (-79 degrees C) to the muscle for 10 s. Muscle was collected from uninjured and injured legs at 3, 10, 24, 48, and 72 h post-injury. qRT-PCR, immunoblotting, and immunohistochemistry were used to quantify/localize MMP-3 and TIMP-1. MMP-3 transcripts increased 19- and 12-fold, 10 and 24 h post-injury (p < 0.01), respectively. TIMP-1 transcript levels increased 9-, 34-, and 60-fold, 10, 24, and 48 h post-injury (p = 0.01), respectively, with a subsequent decrease 72 h post-injury (p < 0.01). Protein levels of the pro-form of MMP-3 increased within 3 h post-injury and remained elevated (p < 0.05). Active MMP-3 decreased over time, reaching a 72% decrease 72 h post-injury (p < 0.05). TIMP-1 protein decreased 75% within 3 h post-injury, returning to baseline by 72 h post-injury. In response to injury, injured skeletal muscle preferentially produces increased levels of the latent form of the MMP-3 protein with a concomitant decrease in the active form, and a significant decrease in TIMP-1 expression. The altered pattern of MMP-3/TIMP-1 expression may be due to alterations in post-transcriptional mechanisms that are responsible for specific regulation of the MMP-3/TIMP-1 system. These data suggest that there is a disproportionate regulation of the MMP-3/TIMP-1 system following traumatic injury and this response may contribute to impaired extracellular matrix remodeling. FAU - Urso, Maria L AU - Urso ML AD - U.S. Army Research Institute of Environmental Medicine, 42 Kansas St, Building 42, Natick, MA 01760, USA. maria.urso@us.army.mil FAU - Szelenyi, Eric R AU - Szelenyi ER FAU - Warren, Gordon L AU - Warren GL FAU - Barnes, Brian R AU - Barnes BR LA - eng PT - Journal Article DEP - 20100327 PL - Germany TA - Eur J Appl Physiol JT - European journal of applied physiology JID - 100954790 RN - 0 (RNA, Messenger) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Animals MH - Male MH - Matrix Metalloproteinase 3/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Models, Animal MH - Muscle, Skeletal/*injuries/*metabolism MH - RNA, Messenger/*metabolism MH - Regeneration MH - Time Factors MH - Tissue Inhibitor of Metalloproteinase-1/*metabolism MH - *Wounds and Injuries EDAT- 2010/03/30 06:00 MHDA- 2010/10/12 06:00 CRDT- 2010/03/30 06:00 PHST- 2010/03/05 00:00 [accepted] PHST- 2010/03/30 06:00 [entrez] PHST- 2010/03/30 06:00 [pubmed] PHST- 2010/10/12 06:00 [medline] AID - 10.1007/s00421-010-1435-5 [doi] PST - ppublish SO - Eur J Appl Physiol. 2010 Jul;109(5):963-72. doi: 10.1007/s00421-010-1435-5. Epub 2010 Mar 27.