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Up-regulation of fibroblast growth factor (FGF) 9 expression and FGF-WNT/β-catenin signaling in laser-induced wound healing

 Zhenlong Zheng  ;  Hye-Young Kang  ;  Sunha Lee  ;  Shin-Wook Kang  ;  Boncheol Goo  ;  Sung Bin Cho 
 WOUND REPAIR AND REGENERATION, Vol.22(5) : 660-665, 2014 
Journal Title
Issue Date
Animals ; Cells, Cultured ; Fibroblast Growth Factor 9/genetics* ; Fibroblast Growth Factor 9/metabolism ; Gene Expression ; Humans ; Keratinocytes/metabolism* ; Lasers, Gas/therapeutic use* ; Mice ; RNA, Messenger/metabolism* ; Real-Time Polymerase Chain Reaction ; Receptor, Fibroblast Growth Factor, Type 2/genetics ; Receptor, Fibroblast Growth Factor, Type 2/metabolism ; Skin/injuries* ; Transforming Growth Factor beta1/genetics ; Transforming Growth Factor beta1/metabolism ; Up-Regulation ; Wnt Proteins/genetics* ; Wnt Proteins/metabolism ; Wnt Signaling Pathway ; Wound Healing/genetics ; Wounds and Injuries/genetics ; Wounds and Injuries/metabolism ; Wounds and Injuries/therapy* ; beta Catenin/genetics* ; beta Catenin/metabolism
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 FGF9 expression and FGF-WNT/β-catenin signaling during wound healing of the skin. We investigated FGF9 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) FGF9 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 FGF9 and FGF9 mRNA. Control NHEKs constitutively expressed FGF9, WNT7b, WNT2, and β-catenin, but did not show Snail or FGF receptor (FGFR) 2 expression. We also found that FGFR2 was significantly induced in NHEKs by rhFGF9 stimulation, and observed that FGFR2 expression was slightly up-regulated on particular days during the wound healing process after ablative laser therapy. Both WNT7b and WNT2 showed up-regulated protein expression during the laser-induced wound healing process in mouse skin; moreover, we discerned that the stimulatory effect of rhFGF9 and rhTGF-β1 activates WNT/β-catenin signaling via WNT7b in cultured NHEKs. Our data indicated that rhFGF9 and/or rhTGF-β1 up-regulate FGFR2, WNT7b, and β-catenin, but not FGF9 and Snail; pretreatment with rh dickkopf-1 significantly inhibited the up-regulation of FGFR2, WNT7b, and β-catenin. Our results suggested that FGF9 and FGF-WNT/β-catenin signaling may play important roles in ablative laser-induced wound healing processes.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
Kang, Hye Young(강혜영)
Zheng, Zhen Long(정진룡)
Cho, Sung Bin(조성빈)
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