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Cyclosporine A up‐regulates S onic hedgehog in gingiva: role of the up‐regulation on gingival cell proliferation
Author(s) -
Chung Y.,
Fu E.
Publication year - 2014
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/jre.12168
Subject(s) - cyclopamine , sonic hedgehog , cell growth , fibroblast , in vivo , proliferating cell nuclear antigen , hedgehog signaling pathway , chemistry , fibroblast activation protein, alpha , microbiology and biotechnology , in vitro , cancer research , biology , signal transduction , medicine , biochemistry , cancer
Background and Objective 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. Material and Methods Here, we investigated SHH expression in gingiva in vitro and in vivo after cyclosporine A treatment and tested the effect of SHH inhibition on cyclosporine A‐enhanced gingival fibroblast proliferation in vitro . Results In human gingival fibroblasts, cyclosporine A treatment increased the expression of SHH 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. Conclusion Cyclosporine A up‐regulates gingival SHH expression in vitro and in vivo , 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.