Flightless I is a key regulator of the fibroproliferative process in hypertrophic scarring and a target for a novel antiscarring therapy

Simple item page
dc.contributor.authorCameron, A.
dc.contributor.authorTurner, C.
dc.contributor.authorAdams, D.
dc.contributor.authorJackson, J.
dc.contributor.authorMelville, E.
dc.contributor.authorArkell, R.
dc.contributor.authorAnderson, P.
dc.contributor.authorCowin, A.
dc.date.issued2016
dc.description.abstractBackground: 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.
dc.description.statementofresponsibilityA.M. Cameron, C.T. Turner, D.H. Adams, J.E. Jackson, E. Melville, R.M. Arkell, P.J. Anderson and A.J. Cowin
dc.identifier.citationBritish Journal of Dermatology, 2016; 174(4):786-794
dc.identifier.doi10.1111/bjd.14263
dc.identifier.issn0007-0963
dc.identifier.issn1365-2133
dc.identifier.orcidAnderson, P. [0000-0002-3730-4652]
dc.identifier.orcidCowin, A. [0000-0003-2885-2080]
dc.identifier.urihttp://hdl.handle.net/2440/100294
dc.language.isoen
dc.publisherWilley-Blackwell
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1038104
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1002009
dc.rights© 2015 British Association of Dermatologists
dc.source.urihttps://doi.org/10.1111/bjd.14263
dc.subjectAnimals
dc.subjectMice, Inbred BALB C
dc.subjectHumans
dc.subjectCicatrix, Hypertrophic
dc.subjectBurns
dc.subjectDisease Models, Animal
dc.subjectCollagen
dc.subjectMicrofilament Proteins
dc.subjectBleomycin
dc.subjectCarrier Proteins
dc.subjectCytoskeletal Proteins
dc.subjectTrans-Activators
dc.subjectReceptors, Cytoplasmic and Nuclear
dc.subjectAntibiotics, Antineoplastic
dc.subjectFemale
dc.subjectTransforming Growth Factor beta1
dc.subjectAntibodies, Neutralizing
dc.subjectMyofibroblasts
dc.titleFlightless I is a key regulator of the fibroproliferative process in hypertrophic scarring and a target for a novel antiscarring therapy
dc.typeJournal article
pubs.publication-statusPublished

Files

Collections

Medicine publications