Cyclosporine A‐induced gingival overgrowth in renal transplant patients accompanied by epithelial‐to‐mesenchymal transition

• Published in: Journal of periodontal research Vol. 58; no. 3; pp. 511 - 519
• Main Authors: Chen, Min Zhi, Dai, Xiao Feng, Sun, Yang, Yu, You Cheng, Yang, Fei
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.06.2023
• Subjects: Creatinine; Cyclosporin A; Cyclosporine - adverse effects; cyclosporine A; Cyclosporins; epithelial‐to‐mesenchymal transition; Gene expression; Gingiva; Gingival Hyperplasia - chemically induced; gingival overgrowth; Gingival Overgrowth - chemically induced; Humans; Hyperplasia; Immunosuppressive Agents - adverse effects; Kidney Transplantation; Kidney transplants; renal transplantation; Reverse transcription; Smad4 protein; cyclosporine A; renal transplantation; gingival overgrowth; epithelial-to-mesenchymal transition
• ISSN: 0022-3484; 1600-0765; 1600-0765
• DOI: 10.1111/jre.13115

Objective To investigate the association between the prevalence of cyclosporin A‐induced gingival overgrowth and the expression of the epithelial‐to‐mesenchymal transition factors in the gingival tissues of renal transplant patients. Background Gingival overgrowth (GO) is a frequent complication in organ transplant patients treated with the immunosuppressant cyclosporin A (CsA). The epithelial‐to‐mesenchymal transition (EMT) is considered a factor contributing to CsA‐induced GO. However, current knowledge on this topic is sparse. Methods Sixty‐three renal transplant patients were divided into two groups according to the occurrence of GO: those with gingival overgrowth (GO+ group) and those without gingival overgrowth (GO− group). Data on age, sex, and use of immunosuppressant and calcium channel blocker medications, serum creatinine values, peak concentrations of blood CsA, and gingival hyperplasia scores were recorded to identify clinically pathogenic factors. Gingival tissues from five patients with CsA‐induced GO and five healthy subjects were selected for histomorphological observation with hematoxylin–eosin staining, Masson staining, and immunohistochemical staining. The mRNA expression of EMT factors was detected with reverse transcription–quantitative PCR. Results The use of CsA significantly increased the prevalence of GO in renal transplant patients. The expression of α‐SMA, SMAD4, and TGM2 was upregulated and that of E‐cadherin was downregulated in the gingival tissues of patients with CsA‐induced GO compared with those of the corresponding controls. Conclusion Treatment with CsA is closely related to the occurrence of GO in renal transplant patients and EMT plays an important role in CsA‐induced gingival tissue hyperplasia.