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

<jats:title>Abstract</jats:title><jats:p>Fibroblast growth factor (<jats:styled-content style="fixed-case">FGF</jats:styled-content>) 9 is secreted by both mesothelial and epithelial cells, and plays important roles in organ development and wound healing via <jats:styled-content style="fixed-case">WNT</jats:styled-content>/β‐catenin signaling. The aim of this study was to evaluate <jats:styled-content style="fixed-case">FGF</jats:styled-content>9 expression and <jats:styled-content style="fixed-case">FGF‐WNT</jats:styled-content>/β‐catenin signaling during wound healing of the skin. We investigated <jats:styled-content style="fixed-case">FGF</jats:styled-content>9 expression and <jats:styled-content style="fixed-case">FGF‐WNT</jats:styled-content>/β‐catenin signaling after laser ablation of mouse skin and adult human skin, as well as in cultured normal human epidermal keratinocytes (<jats:styled-content style="fixed-case">NHEKs</jats:styled-content>) upon stimulation with recombinant human (rh) <jats:styled-content style="fixed-case">FGF</jats:styled-content>9 and rh‐transforming growth factor (<jats:styled-content style="fixed-case">TGF</jats:styled-content>)‐β1. Our results showed that laser ablation of both mouse skin and human skin leads to marked overexpression of <jats:styled-content style="fixed-case">FGF</jats:styled-content>9 and <jats:styled-content style="fixed-case">FGF</jats:styled-content>9 <jats:styled-content style="fixed-case">mRNA</jats:styled-content>. Control <jats:styled-content style="fixed-case">NHEKs</jats:styled-content> constitutively expressed <jats:styled-content style="fixed-case">FGF</jats:styled-content>9, <jats:styled-content style="fixed-case">WNT</jats:styled-content>7<jats:styled-content style="fixed-case">b</jats:styled-content>, <jats:styled-content style="fixed-case">WNT</jats:styled-content>2, and β‐catenin, but did not show Snail or <jats:styled-content style="fixed-case">FGF</jats:styled-content> receptor (<jats:styled-content style="fixed-case">FGFR</jats:styled-content>) 2 expression. We also found that <jats:styled-content style="fixed-case">FGFR</jats:styled-content>2 was significantly induced in <jats:styled-content style="fixed-case">NHEKs</jats:styled-content> by <jats:styled-content style="fixed-case">rhFGF</jats:styled-content>9 stimulation, and observed that <jats:styled-content style="fixed-case">FGFR</jats:styled-content>2 expression was slightly up‐regulated on particular days during the wound healing process after ablative laser therapy. Both <jats:styled-content style="fixed-case">WNT</jats:styled-content>7<jats:styled-content style="fixed-case">b</jats:styled-content> and <jats:styled-content style="fixed-case">WNT</jats:styled-content>2 showed up‐regulated protein expression during the laser‐induced wound healing process in mouse skin; moreover, we discerned that the stimulatory effect of <jats:styled-content style="fixed-case">rhFGF</jats:styled-content>9 and <jats:styled-content style="fixed-case">rhTGF</jats:styled-content>‐β1 activates <jats:styled-content style="fixed-case">WNT</jats:styled-content>/β‐catenin signaling via <jats:styled-content style="fixed-case">WNT</jats:styled-content>7<jats:styled-content style="fixed-case">b</jats:styled-content> in cultured <jats:styled-content style="fixed-case">NHEKs</jats:styled-content>. Our data indicated that <jats:styled-content style="fixed-case">rhFGF</jats:styled-content>9 and/or <jats:styled-content style="fixed-case">rhTGF</jats:styled-content>‐β1 up‐regulate <jats:styled-content style="fixed-case">FGFR</jats:styled-content>2, <jats:styled-content style="fixed-case">WNT</jats:styled-content>7<jats:styled-content style="fixed-case">b</jats:styled-content>, and β‐catenin, but not <jats:styled-content style="fixed-case">FGF</jats:styled-content>9 and Snail; pretreatment with rh dickkopf‐1 significantly inhibited the up‐regulation of <jats:styled-content style="fixed-case">FGFR</jats:styled-content>2, <jats:styled-content style="fixed-case">WNT</jats:styled-content>7<jats:styled-content style="fixed-case">b</jats:styled-content>, and β‐catenin. Our results suggested that <jats:styled-content style="fixed-case">FGF</jats:styled-content>9 and <jats:styled-content style="fixed-case">FGF‐WNT</jats:styled-content>/β‐catenin signaling may play important roles in ablative laser‐induced wound healing processes.</jats:p>