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Altered tissue responsiveness in a murine model of stress-impaired wound healing

Horan, Michael P.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1072267235

Abstract Details

2003, Doctor of Philosophy, Ohio State University, Dentistry.
Research indicated that psychological stress impaired wound closure by >40%. Here, it was hypothesized that stress adversely affected reparative processes during the proliferative phase of healing, leading to impaired wound closure. Data presented herein demonstrate that wound contraction and angiogenesis are significantly impaired in restraint stressed (RST) mice. Contraction was impaired by >46% in RST mice. Fibroblast migration and myofibroblast differentiation, processes important in contraction, were delayed in wounds of RST mice. Real-time PCR and western blot data demonstrated decreased expression of Sm&alphaA, a marker of myofibroblast differentiation. Members of the TGF-β superfamily are thought to regulate fibroblast migration and myofibroblast differentiation. Expression of TGF-&beta1 mRNA was downregulated by >25% (p<0.05) in RST mice, but not the expression of TGF-&beta2 or -&beta3. Although TGF-&beta1 mRNA was reduced in RST mice, no significant differences were detected in active or total TGF-&beta1 protein expression. Thus, the present data indicate that stress delays wound contraction and myofibroblast differentiation through a TGF-&beta-independent mechanism. Data from the present study also indicate reduced microvessel density and hemoglobin content in wounds of RST mice, suggesting impairment of angiogenesis. mRNA expression of angiogenic growth factors, including VEGF, FGF-1, FGF-2, and Ang-2, was downregulated in the wounds of RST mice. Downregulation of VEGF mRNA expression by 35 % on days 3 and 5 post-wounding, translated into reduced protein levels in the wounds of RST mice as indicated by ELISA and western blot analysis. Thus, dysregulation of angiogenic growth factor expression and a diminished angiogenic response during early healing is likely to contribute to the overall impairment of wound healing in RST mice. Since growth factor expression is potentially regulated by endogenous glucocorticoids it was hypothesized that RU486 would restore the kinetics of contraction and closure during early healing in RST mice. In contrast to previous data, these results demonstrated that RU486 was unable to restore early wound healing. Similarly, naltrexone, an opioid receptor antagonist, was also unable to restore healing. Thus, stress-induced impairment of contraction and angiogenesis likely involves a more complex neuroendocrine regulatory pathway than previously thought.
Phillip Marucha (Advisor)
Health Sciences, Dentistry
Wound Healing; Growth Factors; Contraction; Angiogenesis; Stress

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Citations

  • Horan, M. P. (2003). Altered tissue responsiveness in a murine model of stress-impaired wound healing [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1072267235

    APA Style (7th edition)

  • Horan, Michael. Altered tissue responsiveness in a murine model of stress-impaired wound healing. 2003. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1072267235.

    MLA Style (8th edition)

  • Horan, Michael. "Altered tissue responsiveness in a murine model of stress-impaired wound healing." Doctoral dissertation, Ohio State University, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=osu1072267235

    Chicago Manual of Style (17th edition)

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© 2003, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.