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Stress‐Induced Modulation of Matrix Metalloproteinases During Cutaneous Wound Repair
Author(s) -
Gajendrareddy P.K.,
Horan M.P.,
Marucha P.T.
Publication year - 2008
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2005.130215t.x
Subject(s) - matrix metalloproteinase , collagenase , wound healing , interstitial collagenase , gene expression , medicine , pathology , chemistry , immunology , gene , enzyme , biochemistry
Chronic nonhealing wounds have been long associated with an imbalance between the degrading metalloproteinases (MMPs) and their inhibitors (TIMPs). Human and animal studies have shown psychological stress to impair healing and differentially regulate gene expression. We hypothesized that psychological stress‐impaired healing is mediated by altered expression of MMP and TIMP. SKH‐1 mice were subjected to restraint stress 3 days before and 5 days after placement of 3.5 mm biopsy wounds. The wounds were biopsied at various time points and analyzed for gene expression by real‐time PCR. The wounds of stressed mice showed significantly delayed healing when compared to the wounds of controls through day 5 postwounding. There was a significantly higher expression of MMP‐8 in the stressed groups on days 1 (172%, p < 0.0003) and 3 (204%, p < 0.0003) postwounding. Stress decreased MMP‐9 expression on day 5 postwounding (56%, p < 0.02), but showed no significant difference to controls on the other days. TIMP‐1, which is known to inhibit most activated MMPs, had significantly lower expression on day 5 postwounding (56%, p < 0.0003). TIMP‐2, which is constitutively expressed, did not show any difference in expression between the stress and the control groups. During stress, increased MMP‐8 (neutrophil collagenase) activity is in agreement with previous studies in our model that have demonstrated a increase in neutrophil recruitment on days 3 and 5 postwounding. Likewise, lower expression of TIMP‐1 during stress is similar to findings in chronic wounds as opposed to healing surgical wounds. Hence, altered expression of the metalloproteinases and their inhibitors, may lead to increased damage early in healing and decreased repair later in stress‐impaired wound healing. Supported by NIDCR‐P50(DE13749), NIA‐P01(AG16321)