Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/51368
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Type: Journal article
Title: Attenuation of Flightless I, an actin-remodelling protein, improves burn injury repair via modulation of transforming growth factor (TGF)-beta 1 and TGF-beta 3
Author: Adams, D.
Ruzehaji, N.
Strudwick, X.
Greenwood, J.
Campbell, H.
Arkell, R.
Cowin, A.
Citation: British Journal of Dermatology, 2009; 161(2):326-336
Publisher: Blackwell Science Ltd
Issue Date: 2009
ISSN: 0007-0963
1365-2133
Statement of
Responsibility: 
D.H. Adams, N. Ruzehaji, X.L. Strudwick, J.E. Greenwood, H.D. Campbell, R. Arkell and A.J. Cowin
Abstract: <h4>Background</h4>The pathophysiological mechanisms involved in burn injury repair are still not fully understood but include processes involving cellular proliferation, migration and adhesion. The actin cytoskeleton is intricately involved in these key wound repair processes. Flightless I (Flii), an actin-remodelling protein and transcriptional regulator, is an important regulator of wound healing.<h4>Objectives</h4>To investigate the function of Flii gene expression in burn injury repair.<h4>Methods</h4>Partial-thickness scald wounds were created on Flii heterozygous (Flii(+/-)), wild-type (WT) and Flii transgenic (Flii(Tg/+)) mice. Burns were assessed using histology and immunohistochemistry, real-time quantitative polymerase chain reaction and biochemical analysis.<h4>Results</h4>Flii expression, while upregulated in burn injuries, was significantly lower in the wounds of Flii(+/-) vs. WT vs. Flii(Tg/+) mice and healing was improved in Flii(+/-) mice with their burns healing faster than WT and Flii(Tg/+). Pro-scarring transforming growth factor (TGF)-beta1 protein and gene expression were reduced in Flii(+/-) burns while antiscarring TGF-beta3 was significantly elevated. Anti-alpha-smooth muscle actin (alpha-SMA) was decreased in Flii(+/-) burns suggesting a decrease in contractile myofibroblasts in the developing scars. Although Flii is primarily a nuclear and cytoplasmic protein it is also released by wounded cells. Intradermal injection of Flii-neutralizing antibodies (FliAbs) to WT burn wounds significantly improved their healing, indicating a potential novel approach for treating burns. Decreased TGF-beta1 and elevated TGF-beta3 expression were observed in FliAb-treated burns, which may contribute to their observed improvement in healing.<h4>Conclusions</h4>Strategies aimed at reducing Flii expression, for example using neutralizing antibodies, may lead to improved burn outcomes.
Keywords: Animals
Mice, Inbred BALB C
Mice
Burns
Carrier Proteins
Cytoskeletal Proteins
Wound Healing
Down-Regulation
Protein Transport
Female
Transforming Growth Factor beta1
Transforming Growth Factor beta3
Description: The definitive version may be found at www.wiley.com
DOI: 10.1111/j.1365-2133.2009.09296.x
Grant ID: NHMRC
Appears in Collections:Aurora harvest 5
Surgery publications

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