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BioMed Research International
Volume 2013 (2013), Article ID 389792, 9 pages
http://dx.doi.org/10.1155/2013/389792
Research Article

The Influence of Flightless I on Toll-Like-Receptor-Mediated Inflammation in a Murine Model of Diabetic Wound Healing

1Wound Healing Laboratory, Women’s & Children’s Health Research Institute, 72 King William Road, North Adelaide, Adelaide, SA 5006, Australia
2Faculty of Health Sciences, The University of Adelaide, Adelaide, SA 5005, Australia
3Early Mammalian Development Laboratory, Research School of Biological Sciences, Australian National University, Canberra, ACT 2601, Australia

Received 25 October 2012; Revised 7 January 2013; Accepted 7 January 2013

Academic Editor: Jorge Berlanga Acosta

Copyright © 2013 Nadira Ruzehaji et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Impaired wound healing and ulceration represent a serious complication of both type 1 and type 2 diabetes. Cytoskeletal protein Flightless I (Flii) is an important inhibitor of wound repair, and reduced Flii gene expression in fibroblasts increased migration, proliferation, and adhesion. As such it has the ability to influence all phases of wound healing including inflammation, remodelling and angiogenesis. Flii has the potential to modulate inflammation through its interaction with MyD88 which it an adaptor protein for TLR4. To assess the effect of Flii on the inflammatory response of diabetic wounds, we used a murine model of streptozocin-induced diabetes and Flii genetic mice. Increased levels of Flii were detected in Flii transgenic murine wounds resulting in impaired healing which was exacerbated when diabetes was induced. When Flii levels were reduced in diabetic wounds of Flii-deficient mice, healing was improved and decreased levels of TLR4 were observed. In contrast, increasing the level of Flii in diabetic mouse wounds led to increased TLR4 and NF-κB production. Treatment of murine diabetic wounds with neutralising antibodies to Flii led to an improvement in healing with decreased expression of TLR4. Decreasing the level of Flii in diabetic wounds may therefore reduce the inflammatory response and improve healing.