Physiologic levels of epidermal growth factor in saliva stimulate cell migration of an oral epithelial cell line, HO-1-N-1.
An oral epithelial cell line derived from buccal mucosa squamous cell carcinoma, HO-1-N-1, was used to elucidate the role of epidermal growth factor (EGF) in saliva on wound healing of the oral mucosa. The effects of EGF on DNA synthesis, and cell migration was studied and the related signal transduction pathways examined. DNA synthesis by HO-1-N-1 cells was stimulated dose-dependently by 1-10 ng ml(-1) EGF, but significantly inhibited by addition of a PI3-K inhibitor (wortmannin), a p38 MAPK inhibitor (SB203580) or an MEKs inhibitor (PD98059). Cell migration was also accelerated by addition of 1-10 ng ml(-1) EGF; however, the migration rate was decreased to 30% by adding PD98059, to 40% by adding a tyrosine kinase inhibitor (herbimycin A), and to 60% by adding wortmannin or dexamethasone. These results indicate that the physiologic concentration of EGF in saliva may stimulate proliferation and migration of oral epithelial cells for wound healing, when the oral mucosa has been injured. Furthermore, this study revealed that EGF-stimulated signal transduction pathways for epithelial cell proliferation and cell migration are different.
Ohshima
Mitsuhiro
M
Department of Biochemistry, Nihon University School of Dentistry, Tokyo, Japan. oshima-m@dent.nihon-u.ac.jp
Sato
Masashi
M
Ishikawa
Masako
M
Maeno
Masao
M
Otsuka
Kichibee
K
D000730:Androstadienes / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell; D002455:Cell Division; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D004247:DNA / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D018928:Immunity, Mucosal / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009061:Mouth Mucosa / Q000502:physiology*; D009062:Mouth Neoplasms; D012463:Saliva / Q000737:chemistry / Q000502:physiology*; D012471:Salivary Proteins and Peptides / Q000502:physiology*; D014407:Tumor Cells, Cultured; D000077191:Wortmannin; D014945:Wound Healing / Q000502:physiology*
D000730:Androstadienes; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D012471:Salivary Proteins and Peptides; D004815:Epidermal Growth Factor; D003907:Dexamethasone; D004247:DNA; D000077191:Wortmannin