Epithelial and connective tissue cell CTGF/CCN2 expression in gingival fibrosis.

Abstract

Gingival overgrowth is a side effect of certain medications and occurs in non-drug-induced forms either as inherited (human gingival fibromatosis) or idiopathic gingival overgrowth. The most fibrotic drug-induced lesions develop in response to therapy with phenytoin; the least fibrotic lesions are caused by cyclosporin A; and intermediate fibrosis occurs in nifedipine-induced gingival overgrowth. Connective tissue growth factor (CTGF/CCN2) expression is positively related to the degree of fibrosis in these tissues. The present study has investigated the hypothesis that CTGF/CCN2 is expressed in human gingival fibromatosis tissues and contributes to this form of non-drug-induced gingival overgrowth. Histopathology/immunohistochemistry studies showed that human gingival fibromatosis lesions are highly fibrotic, similar to phenytoin-induced lesions. Connective tissue CTGF/CCN2 levels were equivalent to the expression in phenytoin-induced gingival overgrowth. The additional novel observation was made that CTGF/CCN2 is highly expressed in the epithelium of fibrotic gingival tissues. This finding was confirmed by in situ hybridization. Real-time polymerase chain reaction (PCR) analyses of RNA extracted from drug-induced gingival overgrowth tissues for CTGF/CCN2 were fully consistent with these findings. Finally, normal primary gingival epithelial cell cultures were analysed for basal and transforming growth factor beta1 (TGF-beta1) or lysophosphatidic acid-stimulated CTGF/CCN2 expression at protein and RNA levels. These data indicate that fibrotic human gingival tissues express CTGF/CCN2 in both the epithelium and connective tissues; that cultured gingival epithelial cells express CTGF/CCN2; and that lysophosphatidic acid further stimulates CTGF/CCN2 expression. These findings suggest that interactions between epithelial and connective tissues could contribute to gingival fibrosis.

• Authors: A Kantarci, S A Black, C E Xydas, P Murawel, Y Uchida, B Yucekal-Tuncer, G Atilla, G Emingil, M I Uzel, A Lee, E Firatli, M Sheff, H Hasturk, T E Van Dyke, P C Trackman
• Journal: The Journal of pathology (J Pathol) Vol. 210 Issue 1 Pg. 59-66 (Sep 2006) ISSN: 0022-3417 [Print] England
• PMID: 16841303 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Chemical References

• CCN2 protein, human
• Immediate-Early Proteins
• Intercellular Signaling Peptides and Proteins
• Lysophospholipids
• Transforming Growth Factor beta
• Connective Tissue Growth Factor
• lysophosphatidic acid

Topics

• Adult
• Cells, Cultured
• Connective Tissue Cells (chemistry)
• Connective Tissue Growth Factor
• Epithelial Cells (chemistry)
• Fibroblasts (chemistry, pathology)
• Fibromatosis, Gingival (metabolism)
• Fibrosis
• Gingiva (chemistry, pathology)
• Humans
• Immediate-Early Proteins (analysis)
• Immunohistochemistry (methods)
• In Situ Hybridization (methods)
• Intercellular Signaling Peptides and Proteins (analysis)
• Lysophospholipids (metabolism)
• Transforming Growth Factor beta (metabolism)