The study of heat shock protein 47 in cyclosporin A induced gingival overgrowth

• Main Authors: Tsai-Yu, 張采宇
• Other Authors: 張育超
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/93245813188071817722

碩士 === 中山醫學大學 === 牙醫學系碩士班 === 97 === Cyclosporin A (CsA) is used as an immunosuppressive agent and its prominent side effect is the induction of fibrous gingival overgrowth. The progression of fibrous gingival overgrowth results from the accumulation of extracellular matrix (ECM). Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen. HSP47 is consistently and dramatically upregulated in a variety of fibrotic diseases. The aim of this study was to compare HSP47 expression in normal gingival tissues and CsA induced gingival overgrowth specimens and further explore the potential mechanism that may lead to induce HSP47 expression. However, the correlation between HSP47 protein and CsA-induced gingival overgrowth was little known, and it was the main purpose we investigated in this study. Immunohistochemistry was used to compare HSP47 expression between gingival tissues obtained from normal patients and CsA-treated patients in vivo. The evaluations displayed that greater expression of HSP47 was observed on fibroblasts and inflammatory cells in CsA-induced hyperplasia gingive. Reverse transcriptase-polymerase chain reaction、Western blotting were used to determine the effects of CsA on the expression of HSP47 in cultured human gingival fibroblasts in vitro. Furthermore, proinflammatory cytokines interleukin-1α，periodontal pathogen Aggregatibacter actinomycetemcomitans and MEK inhibitor U0126 were added to seek the possible regulatory mechanisms of HSP47 expression. The results indicated that CsA increased expression on the fibroblasts (p<0.05). In CsA-treated fibroblasts, the additions of periodontal pathogens and proinflammatory cytokines significant enlarged the expression of HSP47 (p<0.05), but the additions of U0126 reduced (p<0.05). Taken together, these results suggest that HSP47 expression is significantly up-regulated in gingival tissues of cyclosporin A-treated patients. With periodontal pathogens and proinflammatory cytokines, HSP47 expression was enhanced as compared with additions of CsA alone. The regulation of HSP47 expression induced by cyclosporin A might be critically related with the MEK pathway.