Role of Shh and TGF in cyclosporine-enhanced expression of collagen and α-SMA by gingival fibroblast
Role of Shh and TGF in cyclosporine-enhanced expression of collagen and α-SMA by gingival fibroblast
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DOI：
10.1111/jcpe.12333
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发表时间：
2015-01-01
影响因子：
6.7
通讯作者：
Chiang, Cheng-Yang
中科院分区：
文献类型：
--
作者：
Chung, Yi;Fu, Earl;Chiang, Cheng-Yang
目的环孢素A(CsA)诱导的牙龈过度生长可能是由于造口基质动态平衡的改变所致。Sonic hedgehog(Shh)在胚胎发育和纤维化进展过程中起关键作用，并可能参与CsA改变的牙龈基质内环境。方法采用逆转录聚合酶链式反应和Western印迹分析，检测CsA作用后人牙龈成纤维细胞Shh、1型胶原(Col1)、α-平滑肌肌动蛋白(-SMA)和转化生长因子-β(TGF-β)的mRNA和蛋白表达。结果环孢素A可增强人牙龈成纤维细胞中COL1、SMA、Shh和TGF-α的表达。外源性Shh/TGF-α可促进COL1和-SMA的表达，Shh/TGF-抑制可抑制CsA增强的COL1和-SMA的表达。此外，过量补充外源性转化生长因子-α可增加Shh的mRNA和蛋白表达，而CsA上调的Shh则可被转化生长因子途径抑制剂抑制。然而，外源性Shh和Shh途径抑制剂都不能改变转化生长因子的表达或CsA上调转化生长因子的表达。结论Shh受转化生长因子-1的调节，介导环孢素A改变的牙龈基质内环境平衡。
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.