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Up‐regulation of fibroblast growth factor ( FGF ) 9 expression and FGF‐WNT /β‐catenin signaling in laser‐induced wound healing
Author(s) -
Zheng Zhenlong,
Kang HyeYoung,
Lee Sunha,
Kang ShinWook,
Goo Boncheol,
Cho Sung Bin
Publication year - 2014
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/wrr.12212
Subject(s) - fibroblast growth factor , wnt signaling pathway , microbiology and biotechnology , fibroblast , wound healing , chemistry , catenin , signal transduction , biology , immunology , biochemistry , receptor , in vitro
Fibroblast growth factor ( FGF ) 9 is secreted by both mesothelial and epithelial cells, and plays important roles in organ development and wound healing via WNT /β‐catenin signaling. The aim of this study was to evaluate FGF 9 expression and FGF‐WNT /β‐catenin signaling during wound healing of the skin. We investigated FGF 9 expression and FGF‐WNT /β‐catenin signaling after laser ablation of mouse skin and adult human skin, as well as in cultured normal human epidermal keratinocytes ( NHEKs ) upon stimulation with recombinant human (rh) FGF 9 and rh‐transforming growth factor ( TGF )‐β1. Our results showed that laser ablation of both mouse skin and human skin leads to marked overexpression of FGF 9 and FGF 9 mRNA . Control NHEKs constitutively expressed FGF 9, WNT 7 b , WNT 2, and β‐catenin, but did not show Snail or FGF receptor ( FGFR ) 2 expression. We also found that FGFR 2 was significantly induced in NHEKs by rhFGF 9 stimulation, and observed that FGFR 2 expression was slightly up‐regulated on particular days during the wound healing process after ablative laser therapy. Both WNT 7 b and WNT 2 showed up‐regulated protein expression during the laser‐induced wound healing process in mouse skin; moreover, we discerned that the stimulatory effect of rhFGF 9 and rhTGF ‐β1 activates WNT /β‐catenin signaling via WNT 7 b in cultured NHEKs . Our data indicated that rhFGF 9 and/or rhTGF ‐β1 up‐regulate FGFR 2, WNT 7 b , and β‐catenin, but not FGF 9 and Snail; pretreatment with rh dickkopf‐1 significantly inhibited the up‐regulation of FGFR 2, WNT 7 b , and β‐catenin. Our results suggested that FGF 9 and FGF‐WNT /β‐catenin signaling may play important roles in ablative laser‐induced wound healing processes.