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REGULATION OF MATRIX METALLOPROTEINASE-9 IN CUTANEOUS
WOUND HEALING
by
Wesley Andrew Grimm
__________________________________________________________________
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(EXPERIMENTAL AND MOLECULAR PATHOLOGY)
December 2008
Copyright 2008 Wesley Andrew
Grimm
Object Description
| Title | Regulation of matrix metalloproteinase-9 in cutaneous wound healing |
| Author | Grimm, Wesley Andrew |
| Author email | wes.grimm@gmail.com; wgrimm@usc.edu |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Experimental & Molecular Pathology |
| School | Keck School of Medicine |
| Date defended/completed | 2008-08-13 |
| Date submitted | 2008 |
| Restricted until | Unrestricted |
| Date published | 2008-11-20 |
| Advisor (committee chair) | Han, Yuan-Ping |
| Advisor (committee member) |
Garner, Warren Chuong, Cheng-Ming |
| Abstract | BACKGROUND: Matrix metalloproteinases (MMPs) represent a family of zinc-dependent proteases that contain a conserved pro-peptide domain. MMP-9 is a gelatinase known for degrading type IV collagen among its potential substrates. MMP-9 is implicated in a myriad of different biological processes and pathologies such as wound healing, and cancer. Thus, strict transcriptional and post-translational regulation of MMP-9 is important. Latent pro-MMPs have a conserved mechanism of activation, which is indicated by the conversion from a 92kDa to 82kDa isoform. However, the tissue specific mechanisms of MMP-9 activation are not clear. In addition, the functions of different isoforms have not been elaborated in the context of different biological processes. AIMS: Therefore, we seek to characterize the mechanism of MMP-9 activation in human skin during the inflammatory state, and describe the functional roles of MMP-9 in wound healing. RESULTS: MMP-9 is expressed in human wounds and is associated with inflammation. This observation can be partially recapitulated in multiple animal models, showing robust MMP-9 expression and activation. Further, MMP-9 mRNA expression is directly controlled by inflammatory cytokine, TNF-alpha, in human skin explant and cell culture of epidermal keratinocytes. Protein expression shows similar regulation, however, MMP-9 activation does not occur in cell culture. Incubation of purified pro-MMP-9 with skin extract results in multiple MMP-9 cleavage products and stable MMP-9 activation. These products can be produced in quantities that are sufficient for N-terminal Edman degradation. CONCLUSIONS: MMP-9 activation is a prominent characteristic of inflammation and wound healing. |
| Keyword | MMP; matrix metalloproteinase; wound healing; MMP-9; MMP9; MMP activation |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m1809 |
| Contributing entity | University of Southern California |
| Rights | Grimm, Wesley Andrew |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Grimm-2402 |
| Archival file | uscthesesreloadpub_Volume17/etd-Grimm-2402.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Full text | REGULATION OF MATRIX METALLOPROTEINASE-9 IN CUTANEOUS WOUND HEALING by Wesley Andrew Grimm __________________________________________________________________ A Thesis Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (EXPERIMENTAL AND MOLECULAR PATHOLOGY) December 2008 Copyright 2008 Wesley Andrew Grimm |
