The upregulation of heat shock protein 47 in human gingival fibroblasts stimulated with cyclosporine A

Chang T‐Y, Tsai C‐H, Chang Y‐C. The upregulation of heat shock protein 47 in human gingival fibroblasts stimulated with cyclosporine A. J Periodont Res 2010; 45: 317–322. © 2009 John Wiley & Sons A/S Background and Objective: Heat shock protein 47 (Hsp47), a collagen‐specific molecular chaperone, is involved in the processing and/or secretion of procollagen. Heat shock protein 47 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 cyclosporine A‐induced gingival overgrowth specimens and further explore the potential mechanisms that may lead to induction of Hsp47 expression. Material and Methods: Fifteen cyclosporine A‐induced gingival overgrowth specimens and five normal gingival tissues were examined by immunohistochemistry. Western blot was used to investigate the effects of cyclosporine A on the expression of Hsp47 in human gingival fibroblasts. In addition, Aggregatibacter actinomycetemcomitans, interleukin‐1α (IL‐1α) and mitogen‐activated protein kinase kinase (MEK) inhibitor U0126 were added to seek the possible regulatory mechanisms of Hsp47 expression. Results: A significantly higher percentage of cells positively stained for Hsp47 was noted in the cyclosporine A‐induced gingival overgrowth group than in the normal gingival group (p < 0.05). Expression of Hsp47 was observed mainly in the cytoplasm of fibroblasts, endothelial cells, epithelial cells and inflammatory cells. Expression of Hsp47 was significantly higher in cyclosporine A‐induced gingival overgrowth specimens with higher levels of inflammatory infiltrates (p < 0.05). Cyclosporine A upregulated Hsp47 expression in human gingival fibroblasts in a dose‐dependent manner (p < 0.05). The addition of A. actinomycetemcomitans or interlukin‐1α significantly increased Hsp47 expression compared with cyclosporine A alone (p < 0.05). The MEK inhibitor U0126 was found to inhibit cyclosporine A‐induced Hsp47 expression (p < 0.05). Conclusion: Expression of Hsp47 is significantly upregulated in cyclosporine A‐induced gingival overgrowth specimens, and Hsp47 expression induced by cyclosporine A in fibroblasts may be mediated by the MEK signal transduction pathway. The expression of Hsp47 could be significantly enhanced by A. actinomycetemcomitans and interlukin‐1α.