Expression of fibronectin-binding integrins in gingival epithelium in drug-induced gingival overgrowth.
OBJECTIVE
Gingival overgrowth is a side-effect of nifedipine and cyclosporin medications. Integrins are transmembrane glycoproteins that mediate cell adhesion, regulate cell proliferation and participate in the regulation of tissue fibrosis. The aim of this study was to investigate whether expression of epithelial cell integrins is linked to the development of drug-induced gingival overgrowth.


METHODS
Human gingival biopsies of patients taking nifedipine, cyclosporin, or a combination of both medications, were used. Expression of the alpha5beta1, alphavbeta1 and alphavbeta6 integrins, and of cellular extra domain A of fibronectin, was localized in frozen sections using immunohistochemistry.


RESULTS
The activated conformation of the beta1, alpha5beta1 and alphavbeta6 integrins were more frequently expressed in distinct locations in the oral epithelium in the combined drug group. Cellular extra domain A of fibronectin, a ligand for both alpha5beta1 and alphavbeta6 integrins, was expressed within the connective tissue of all groups. It was also expressed around the basal keratinocytes of the control, nifedipine and cyclosporin-induced gingival overgrowth groups, but not in the combined medication group. No relationship between the presence of inflammation and integrin expression was found.


CONCLUSIONS
The results indicate that expression of certain integrins is up-regulated in the epithelium of drug-induced gingival overgrowth where they could participate in controlling the formation of elongated rete ridges and tissue fibrosis.
Walsh
P
P
Faculty of Dentistry, University of British Columbia, Vancouver, Canada.
Häkkinen
L
L
Pernu
H
H
Knuuttila
M
M
Larjava
H
H
D000328:Adult; D000704:Analysis of Variance; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D002121:Calcium Channel Blockers / Q000009:adverse effects; D016572:Cyclosporine / Q000009:adverse effects; D004338:Drug Combinations; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005881:Gingiva / Q000378:metabolism; D019214:Gingival Overgrowth / Q000139:chemically induced* / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D039081:Integrin alpha5beta1 / Q000096:biosynthesis; D019012:Integrin beta1 / Q000096:biosynthesis; D016023:Integrins / Q000096:biosynthesis*; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D009543:Nifedipine / Q000009:adverse effects; D018709:Statistics, Nonparametric; D015854:Up-Regulation
D000951:Antigens, Neoplasm; D002121:Calcium Channel Blockers; D004338:Drug Combinations; D005353:Fibronectins; D007166:Immunosuppressive Agents; D039081:Integrin alpha5beta1; D019012:Integrin beta1; D016023:Integrins; C073878:integrin alphavbeta6; D016572:Cyclosporine; D009543:Nifedipine