Role of Shh and TGF in cyclosporine-enhanced expression of collagen and α-SMA by gingival fibroblast

ObjectiveCyclosporine-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. MethodsUsing 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 (-SMA) and transforming growth factor-beta (TGF-) 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-. ResultsCyclosporine-A enhanced COL1, -SMA, Shh and TGF- expressions in human gingival fibroblasts. The exogenous Shh/TGF- augmented the expression of COL1 and -SMA, and the Shh/TGF- inhibition suppressed the CsA-enhanced COL1 and -SMA expressions. Moreover, Shh mRNA and protein expressions increased if extra-supplementing the exogenous TGF-, whereas the CsA-upregulated Shh was mitigated by the TGF- pathway inhibitor. However, neither exogenous Shh nor the Shh pathway inhibitor alters TGF- expression or CsA-up-regulated TGF- expression. ConclusionsShh, regulated by TGF-, mediates CsA-altered gingival matrix homeostasis.