Epithelial and connective tissue cell CTGF/CCN2 expression in gingival fibrosis.
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.
Kantarci
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Department of Periodontology and Oral Biology, Boston University, Goldman School of Dental Medicine, 700 Albany Street, Boston, MA 02118, USA.
Black
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Xydas
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Murawel
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Uchida
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Yucekal-Tuncer
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Atilla
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Emingil
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Uzel
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Lee
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Firatli
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Sheff
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Hasturk
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Van Dyke
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Trackman
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D000328:Adult; D002478:Cells, Cultured; D003239:Connective Tissue Cells / Q000737:chemistry*; D055513:Connective Tissue Growth Factor; D004847:Epithelial Cells / Q000737:chemistry; D005347:Fibroblasts / Q000737:chemistry / Q000473:pathology; D005351:Fibromatosis, Gingival / Q000378:metabolism*; D005355:Fibrosis; D005881:Gingiva / Q000737:chemistry / Q000473:pathology; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis*; D008246:Lysophospholipids / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008246:Lysophospholipids; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; C032881:lysophosphatidic acid