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https://hdl.handle.net/2440/43145
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Type: | Journal article |
Title: | Collagen loss and impaired wound healing is associated with c-Myb deficiency |
Author: | Kopecki, Z. Luchetti, M. Adams, D. Strudwick, X. Mantamadiotis, T. Stoppacciaro, A. Gabrielli, A. Ramsay, R. Cowin, A. |
Citation: | Journal of Pathology, 2007; 211(3):351-361 |
Publisher: | John Wiley & Sons Ltd |
Issue Date: | 2007 |
ISSN: | 0022-3417 1096-9896 |
Statement of Responsibility: | Z Kopecki, MM Luchetti, DH Adams, X Strudwick, T Mantamadiotis, A Stoppacciaro, A Gabrielli, RG Ramsay, AJ Cowin |
Abstract: | Collagen type I serves as an abundant structural and signalling component of skin. It is also an established target gene of the transcription factor, c-Myb. When c-myb-/- embryos were examined it was observed that their skin was markedly thinner than normal. Importantly, immunohistochemical investigation showed complete absence of collagen type I. Although these homozygous knock-out embryos fail to develop beyond day 15, fibroblasts established from these embryos (mouse embryonic fibroblasts [MEFs]) show defective proliferative responses. Furthermore, in vitro scratch wound assays demonstrated that these c-myb-/- MEFs also exhibit slower closure than their wild-type counterparts. Embryonic lethality has meant that examination of the role of c-Myb in adult mouse skin has not been reported to date. However, in view of the abundance of collagen type I in normal skin, its role in skin integrity and the in vitro data showing proliferative and migration defects in c-myb-/- MEFs, we investigated the consequences of heterozygous c-myb loss in adult mice on the complex process of skin repair in response to injury. Our studies clearly demonstrate that heterozygous c-myb deficiency has a functional effect on wound repair, collagen type I levels and, in response to wounding, transforming growth factor-beta1 (an important collagen stimulating factor) induction expression is aberrantly high. Manipulation of c-Myb may therefore provide new therapeutic opportunities for improving wound repair while uncontrolled expression may underpin some fibrotic disorders. |
Keywords: | c-myb collagen TGF-β1 wound healing fibrosis |
Rights: | Copyright © 2007 Pathological Society of Great Britain and Ireland. |
DOI: | 10.1002/path.2113 |
Published version: | http://dx.doi.org/10.1002/path.2113 |
Appears in Collections: | Aurora harvest Paediatrics publications |
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