Cameron, A.Turner, C.Adams, D.Jackson, J.Melville, E.Arkell, R.Anderson, P.Cowin, A.2016-08-042016-08-042016British Journal of Dermatology, 2016; 174(4):786-7940007-09631365-2133http://hdl.handle.net/2440/100294Background: Hypertrophic scarring carries a large burden of disease, including disfigurement, pain and disability. There is currently no effective medical treatment to reduce or prevent hypertrophic scarring. Flightless I (Flii), a member of the gelsolin family of actin remodelling proteins, is an important negative regulator of wound repair. Objectives: The objective of this study was to investigate the role of Flii as a potential regulator of hypertrophic scarring. Methods: Using human skin samples and an animal model of bleomycin-induced hypertrophic scarring in mice that overexpress or have reduced expression of Flii, we investigated its effect on dermal fibrosis and hypertrophic scarring. Results: Flii expression was increased in human burns and hypertrophic scars. A similar increase in Flii was observed in hypertrophic scars formed in mice post-treatment with bleomycin. However, Flii-deficient (Flii+/−) mice had reduced scarring in response to bleomycin evidenced by decreased dermal thickness, smaller cross-sectional scar areas, fewer myofibroblasts and a decreased collagen I/III ratio. In contrast, bleomycin-treated Flii-overexpressing mice (FliiTg/Tg) showed increased scar dermal thickness, larger cross-sectional scar areas, more myofibroblasts and an increased collagen I/III ratio. Injecting developing scars with a Flii neutralizing antibody led to a significant reduction in the size of the scars and a reduction in the collagen I/III ratio. Conclusion: This study identifies Flii as a profibrotic agent that contributes to excessive scar formation. Reducing its activity using neutralizing antibodies is a promising approach for reducing hypertrophic scarring.en© 2015 British Association of DermatologistsAnimalsMice, Inbred BALB CHumansCicatrix, HypertrophicBurnsDisease Models, AnimalCollagenMicrofilament ProteinsBleomycinCarrier ProteinsCytoskeletal ProteinsTrans-ActivatorsReceptors, Cytoplasmic and NuclearAntibiotics, AntineoplasticFemaleTransforming Growth Factor beta1Antibodies, NeutralizingMyofibroblastsJournal article003004198310.1111/bjd.142630003753311000462-s2.0-84953774766218440Anderson, P. [0000-0002-3730-4652]Cowin, A. [0000-0003-2885-2080]