Role of Shh and TGF in cyclosporine-enhanced expression of collagen and α-SMA by gingival fibroblast.
OBJECTIVE
Cyclosporine-A (CsA)-induced gingival overgrowth may arise from an alteration in stoma matrix homeostasis. Sonic hedgehog (Shh) plays a key role during embryogenic development and fibrotic progression, and may be involved in CsA-altered gingival matrix homeostasis.


METHODS
Using the reverse transcription-polymerase chain reaction and Western blot analysis, we investigated the mRNA and protein expressions of Shh, type 1 collagen (COL1), alpha-smooth muscle actin (α-SMA) and transforming growth factor-beta (TGF-β) in human gingival fibroblasts after CsA treatments. The effect of Shh on CsA-induced alterations was further evaluated by the extra-supplement or inhibition of Shh or TGF-β.


RESULTS
Cyclosporine-A enhanced COL1, α-SMA, Shh and TGF-β expressions in human gingival fibroblasts. The exogenous Shh/TGF-β augmented the expression of COL1 and α-SMA, and the Shh/TGF-β inhibition suppressed the CsA-enhanced COL1 and α-SMA expressions. Moreover, Shh mRNA and protein expressions increased if extra-supplementing the exogenous TGF-β, whereas the CsA-upregulated Shh was mitigated by the TGF-β pathway inhibitor. However, neither exogenous Shh nor the Shh pathway inhibitor alters TGF-β expression or CsA-up-regulated TGF-β expression.


CONCLUSIONS
Shh, regulated by TGF-β, mediates CsA-altered gingival matrix homeostasis.
Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan.
Yi
Y
Chung
Earl
E
Fu
Yu-Tang
YT
Chin
Hsiao-Pei
HP
Tu
Hsien-Chung
HC
Chiu
E-Chin
EC
Shen
Cheng-Yang
CY
Chiang
D000199:Actins / Q000187:drug effects*; D018929:Cell Culture Techniques; D002460:Cell Line; D024042:Collagen Type I / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects*; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020239:Receptor Cross-Talk / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology; D014704:Veratrum Alkaloids / Q000494:pharmacology
C541116:ACTA2 protein, human; D000199:Actins; D024042:Collagen Type I; D053823:Hedgehog Proteins; D007166:Immunosuppressive Agents; C509239:SHH protein, human; D016212:Transforming Growth Factor beta; D014704:Veratrum Alkaloids; D016572:Cyclosporine; C000541:cyclopamine
Sonic hedgehog; collagen; cyclosporine-A; gingival fibroblasts; transforming growth factor-beta