Increased HSP47 expression in human gingival fibroblasts by cyclosporin A

Objectives: 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. However, there is little known about the correlation between HSP47 and cyclosporin A (CsA)-induced gingival overgrowth. The aim of this study was to investigate the effects of CsA on the expression of HSP47 in human gingival fibroblasts (HGFs) in vitro and further to compare HSP47 expression in normal healthy gingival tissues and CsA-induced gingival overgrowth specimens in vivo. Methods: Ten CsA-induced gingival overgrowth specimens and five normal gingival tissues were examined by immunohistochemistry. The reverse-transcriptase polymerase chain reaction was used to investigate the effects on HGFs exposed to cyclosporin A. Results: The HSP47 staining in gingival tissue was stronger in CsA-induced gingival overgrowth group than normal gingival group (p<0.05). Intensive staining for HSP47 expression was observed mainly in the cytoplasm of fibroblasts, endothelial cells, and inflammatory cells. In addition, CsA was found to increase HSP47 expression in HGFs in a dose-dependent manner (p<0.05). The amount of HSP47 was highest at a concentration level of 200 ng/ml CsA. CsA was also found to increase HSP47 expression in HGFs in a time-dependent manner (p<0.05). Conclusions: These results suggest that HSP47 expression is significantly upregulated in CsA-induced gingival overgrowth specimens and CsA may be responsible for the enhanced HSP47 expression in vivo.