MMP-8 overexpression and persistence of neutrophils relate to stress-impaired healing and poor collagen architecture in mice.

Brain Behav Immun

Department of Periodontics, University of Illinois at Chicago, College of Dentistry, 801 S. Paulina St., MC 859, Chicago, IL 60612, USA.

Published: February 2013

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) are critical for tissue remodeling during wound repair. Psychological stress has been found to impair wound healing in humans and animals. The objective of this study was to assess MMP and TIMP gene expression during stress-impaired healing. Female SKH-1 mice (n=299) were divided into control and stress groups (13h restraint/day for 3days prior to and 5days post-wounding). Two 3.5mm cutaneous full-thickness wounds were placed on the dorsum of each mouse and wound measurements were performed daily. RT-PCR for gene expression of MMP-2, MMP-8, MMP-9, TIMP-1 and TIMP-2 was performed at days 1, 3 and 5. Immunohistochemical analyses of the healed wounds were performed at days 15 and 28. As expected, wounds healed more slowly in restraint-stressed mice compared to controls. Stressed mice exhibited MMP-8 overexpression and lower TIMP-1 levels during healing, and poorer collagen organization once healed. MMP-8 overexpression may have stemmed from a higher level of neutrophils, observed in wound tissue on days 3 and 5. These findings implicate higher neutrophil numbers, MMP-8 overexpression, and TIMP-1 under-expression, as mechanisms that may compromise wound outcomes such as scarring under conditions of stress.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878435PMC
http://dx.doi.org/10.1016/j.bbi.2012.10.016DOI Listing

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