Defense Date

2000

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Anatomy & Neurobiology

First Advisor

Oliver Bögler

Abstract

The biochemical and physiologic mechanisms responsible for excisional wound contraction have been extensively studied but are not completely understood. Furthermore, the genes that regulate these processes are unknown. As a result, there are limited treatment options available for patients with diseases or conditions characterized by abnormal tissue contraction. In an attempt to improve our understanding of these mechanisms and identify some of the putative regulatory genes, we studied excisional wound healing in the mid-gestational fetal rabbit. These wounds normally do not contract nor are they associated with inflammation, fibrosis, or scar formation. However, we have been able to induce contraction, with and without inflammation and fibrosis, by providing sustained levels of exogenous TGF-βl and -β3, respectively, at the excisional wound site. In addition to learning more about the role of the TGF-β isoforms in tissue repair, we utilized our model to identify some of the regulatory genes responsible for contraction.

We theorized that homeobox genes direct the mechanisms of excisional wound contraction. These genes encode for a family of transcription factors that are known to regulate cellular differentiation and tissue migration during development. We demonstrated that homeobox genes are expressed in normal fetal and adult rabbit skin and their pattern of expression varies for several of these genes. There was a 2-fold increase for Hoxa-5, yet a moderate decrease in Hoxc-6 transcripts in the contracting versus non-contracting fetal group. In addition, there was a greater than 3-fold increase in Hoxd-8 transcripts in the adult excisional wound group compared to the normal adult skin group. Using a ribonuclease protection assay, we confirmed that the level of Hoxd-8 expression was significantly greater at the site of adult excisional wounds than in the normal skin. These findings suggest that this homeobox gene may regulate some aspect of the mechanisms responsible for excisional wound contraction. Further studies may delineate the role of Hoxa-8 and other homeobox genes in the mechanisms of excisional wound contraction. If they are determined to direct various aspects of the contractile process, future therapeutic interventions targeting these genes may improve the healing of many abnormal wound healing conditions and diseases.

Comments

Scanned, with permission from the author, from the original print version, which resides in University Archives.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

11-28-2017

Included in

Anatomy Commons

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