Cyclosporine A up‐regulates Sonic hedgehog in gingiva: role of the up‐regulation on gingival cell proliferation. (14th May 2014)

• Record Type: Journal Article
• Authors: Chung, Y.; Fu, E.
• Is Part Of: Journal of periodontal research. Volume 49:Number 6(2014:Dec.)
• Page Start: 810
• Page End: 816
• Publication Date: 2014-05-14
• Subjects: Periodontics -- Periodicals; 617.632
• DOI: 10.1111/jre.12168
• Languages: English
• ISSNs: 0022-3484

Abstract

<abstract abstract-type="main" id="jre12168-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="jre12168-sec-0001" sec-type="section"> <title>Background and Objective</title> <p>Sonic hedgehog protein (SHH) is a mitogen that stimulates cell proliferation. Cyclosporine A enhances the proliferation of gingival cells; however, the relationships of SHH to cyclosporine A or to cyclosporine A‐enhanced gingival cell proliferation have not been described.</p> </sec> <sec id="jre12168-sec-0002" sec-type="section"> <title>Material and Methods</title> <p>Here, we investigated SHH expression in gingiva <italic>in vitro</italic> and <italic>in vivo</italic> after cyclosporine A treatment and tested the effect of SHH inhibition on cyclosporine A‐enhanced gingival fibroblast proliferation <italic>in vitro</italic>.</p> </sec> <sec id="jre12168-sec-0003" sec-type="section"> <title>Results</title> <p>In human gingival fibroblasts, cyclosporine A treatment increased the expression of <italic>SHH</italic> transcripts and SHH protein, and stimulated cell proliferation; the addition of cyclopamine, an SHH signaling inhibitor, suppressed cyclosporine A‐enhanced cell proliferation. Up‐regulated expression of SHH and up‐regulation of proliferating cell nuclear antigen transcripts and protein were observed in the edentulous gingiva of cyclosporine A‐treated rats.</p> </sec> <sec id="jre12168-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Cyclosporine A up‐regulates gingival SHH expression <italic>in vitro</italic> and <italic>in vivo</italic>, and the inhibition of the SHH pathway counteracts the stimulatory effect of cyclosporine A on gingival fibroblast proliferation. Therefore, we suggest that SHH mediates a novel molecular mechanism for cyclosporine A‐induced gingival complications.</p> </sec> </abstract>