Keratinocyte growth factor promotes cell motility during alveolar epithelial repair in vitro.
Epithelia play a key role as protective barriers, and mechanisms of repair are crucial for restoring epithelial barrier integrity, especially in the lung. Cell spreading and migration are the first steps of reepithelialization. Keratinocyte growth factor (KGF) plays a key role in lung epithelial repair and protects against various injuries. We hypothesized that KGF may protect the lung not only by inducing proliferation but also by promoting epithelial repair via enhanced epithelial cell migration. In an in vitro wound-healing model, we found that KGF enhanced wound closure by 33%. KGF acted primarily by inducing lamellipodia emission (73.2 +/- 3.9% of KGF-treated cells had lamellipodia vs 61.3 +/- 3.4% of control cells) and increasing their relative surface area (59 +/- 2.7% with KGF vs 48 +/- 2.0% in controls). KGF reduced cytoskeleton stiffness as measured by magnetic twisting cytometry and increased cell motility (5.8 +/- 0.42 microm/h with KGF vs 3.7 +/- 0.41 microm/h in controls). KGF-increased cell motility was associated with increased fibronectin deposition during wound closure and with fibronectin reorganization into fibrils at the rear of the cells. Taken together, our findings strongly suggest that KGF may promote epithelial repair through several mechanisms involved in cell migration.
Galiacy
Stéphane
S
Unité INSERM U492, Faculté de Médecine, 8 rue du Général Sarrail, 94010 Créteil, France. s.galiacy@cellbio.duke.edu
Planus
Emmanuelle
E
Lepetit
Hélène
H
Féréol
Sophie
S
Laurent
Valérie
V
Ware
Lorraine
L
Isabey
Daniel
D
Matthay
Michael
M
Harf
Alain
A
d'Ortho
Marie Pia
MP
D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D005353:Fibronectins / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011650:Pulmonary Alveoli / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects*
D000199:Actins; C496455:Fgf7 protein, rat; D005353:Fibronectins; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors