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Analysis of cells and matrix in cyclosporine-induced gingival overgrowth Nouri, Masoumeh


Background and objective: Gingival overgrowth is one of the side effects of cyclosporine A, an immunosuppressant agent. Cyclosporine A is used clinically to counteract rejection following organ transplantation. The aim of the present study was to characterize the tissue changes that occur in gingival tissue in patients receiving this medication, compared to control patients' tissues. -Materials and Methods: Gingival biopsies were taken from 18 kidney transplant patients referred to Labafi hospital in Tehran/ Iran. Periodontal flap approach was a part of the procedure to treat their gingival overgrowth. In order to compare these samples with normal tissues, 12 gingival tissue samples were obtained from healthy individuals in the process of crown lengthening that took part in the school of dentistry in SHB University, Tehran/ Iran. The patients from the two groups were as sex and age-matched as much as possible. In all cases, patients gave informed consent for the use of their tissue samples for research. Tissue collection, fixation, histological and histochemical stainings were performed under the same conditions in both groups. The antibodies utilized for immunohistochemical stainings comprised of 1A4, PCNA, LC2, 2B1 and CD44. These antibodies target α-smooth muscle actin, proliferating cells, c terminal and core of versican and hyaluronan receptors, respectively. -Results: Compared to controls, histological features from gingival overgrowth samples revealed changed retepegs, some degrees of acanthosis, hyperkeratosis and parakeratosis, increased vascularization, and severe inflammatory infiltration. The inflammatory infiltrate included high number of macrophages. Matrix changes included prominent accumulation of glycosaminoglycans (GAGs) and proteoglycans (mainly versican). Conclusion: Both epithelium and connective tissue showed changes in gingival overgrowth samples. Gingival overgrowth tissues showed increased inflammation in which CD44 positive cells (macrophages) predominated. More proliferative activity and changes in retepegs were observed in epithelium. The presence of myofibroblasts was noted in connective tissue. Versican accumulation was also observed in connective tissue, in gingival overgrowth samples. Our studies are consistent with a macrophage-driven accumulation of versican-rich connective tissue, associated with epithelial proliferation in gingival overgrowth, secondary to cyclosporine therapy.

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