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Fibroblast‐specific upregulation of F lightless I impairs wound healing
Author(s) -
Turner Christopher T.,
Waters James M.,
Jackson Jessica E.,
Arkell Ruth M.,
Cowin Allison J.
Publication year - 2015
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12751
Subject(s) - downregulation and upregulation , wound healing , fibroblast , microbiology and biotechnology , myofibroblast , inflammation , chemistry , biology , immunology , pathology , medicine , in vitro , biochemistry , fibrosis , gene
The cytoskeletal protein Flightless (Flii) is a negative regulator of wound healing. Upregulation of Flii is associated with impaired migration, proliferation and adhesion of both fibroblasts and keratinocytes. Importantly, Flii translocates from the cytoplasm to the nucleus in response to wounding in fibroblasts but not keratinocytes. This cell‐specific nuclear translocation of Flii suggests that Flii may directly regulate gene expression in fibroblasts, providing one potential mechanism of action for Flii in the wound healing response. To determine whether the tissue‐specific upregulation of Flii in fibroblasts was important for the observed inhibitory effects of Flii on wound healing, an inducible fibroblast‐specific Flii overexpressing mouse model was generated. The inducible ROSA 26 system allowed the overexpression of Flii in a temporal and tissue‐specific manner in response to tamoxifen treatment. Wound healing in the inducible mice was impaired, with wounds at day 7 postwounding significantly larger than those from non‐inducible controls. There was also reduced collagen maturation, increased myofibroblast infiltration and elevated inflammation. The impaired healing response was similar in magnitude to that observed in mice with non‐tissue‐specific upregulation of Flii suggesting that fibroblast‐derived Flii may have an important role in the wound healing response.