title: Cyclosporin A-induced gingival overgrowth is not associated with myofibroblast transdifferentiation.
abstract: Cyclosporin A (CyA) induces gingival overgrowth via its stimulatory effects on expression of transforming growth factor-beta1 (TGF-beta1) and collagen. It is not known whether CyA has a direct effect on gingival fibroblasts or induces its effect indirectly via stimulation of myofibroblast transdifferentiation. The present study was undertaken to examine the in vivo and in vitro effect of CyA on myofibroblast transdifferentiation. Rats were treated for 60 days with a daily subcutaneous injection of CyA, and the gingival overgrowth tissue was analyzed by immunohistochemistry. In vitro, fibroblasts from normal gingiva (NG) were cultured in the presence of different concentrations of CyA, and subjected to semi-quantitative reverse transcriptase-polymerase chain reaction and western blot. Although CyA treatment stimulated TGF-beta1 expression by NG fibroblasts, it lacked to induce expression and production of isoform alpha of smooth muscle actin (alpha-SMA), the specific myofibroblast marker. The expression levels of connective tissue growth factor (CTGF), which has been considered a key molecule to promote the transdifferentiation of myofibroblasts via TGF-beta1 activation, were unaffected by CyA. Our results demonstrate that CyA-induced gingival overgrowth is not associated with activation of myofibroblast transdifferentiation, since CyA is not capable to increase CTGF expression.
authors.affiliation: Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil. lays.sobral@gmail.com
authors.forename: Lays Martin
authors.initials: LM
authors.lastname: Sobral
authors.forename: Michele Gassen
authors.initials: MG
authors.lastname: Kellermann
authors.forename: Edgard
authors.initials: E
authors.lastname: Graner
authors.forename: Hercilio
authors.initials: H
authors.lastname: Martelli-Junior
authors.forename: Ricardo Della
authors.initials: RD
authors.lastname: Coletta
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D054338:Cell Transdifferentiation / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000032:analysis / Q000378:metabolism*; D003470:Culture Media; D016572:Cyclosporine / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019214:Gingival Overgrowth / Q000139:chemically induced* / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000378:metabolism
chemical_list: D000199:Actins; D003094:Collagen; D055513:Connective Tissue Growth Factor; D003470:Culture Media; D016572:Cyclosporine; D007166:Immunosuppressive Agents; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat