TGF-β Signaling in Gingival Fibroblast-Epithelial Interaction
TGF-β Signaling in Gingival Fibroblast-Epithelial Interaction
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DOI：
10.1177/0022034510378423
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发表时间：
2010-11-01
影响因子：
7.6
通讯作者：
Kappert, K.
中科院分区：
文献类型：
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作者：
Ohshima, M.;Yamaguchi, Y.;Kappert, K.
可逆性牙龈炎转变为不可逆性牙周炎的潜在机制和治疗方案尚不清楚。由于转化生长因子（TGF）-β与牙龈成纤维细胞中差异调节的基因表达有关，因此我们假设TGF-β信号在受牙周炎影响的牙龈中被激活，沿着胶原蛋白降解增强，而胶原蛋白降解增强可被TGF-β抑制逆转。应用一种新的三维（3D）凝胶培养系统，包括原代人牙龈成纤维细胞（GF）和牙龈上皮细胞（GE）在胶原凝胶。严重牙周炎患者的GF群降解胶原凝胶，TGF-β受体激酶抑制剂可降低胶原凝胶。在GF/GE共培养物中，TGF-β反应基因的上调是明显的。此外，TGF-β下游传感器Smad 3C在牙周炎影响的牙龈和3D文化高度磷酸化。这些结果表明，TGF-β信号参与牙周炎中成纤维细胞-上皮细胞的相互作用，并表明三维培养系统是一个有用的体外模型，用于牙周炎的治疗药物筛选。
The underlying mechanism and the therapeutic regimen for the transition of reversible gingivitis to irreversible periodontitis are unclear. Since transforming growth factor (TGF)-beta has been implicated in differentially regulated gene expression in gingival fibroblasts, we hypothesized that TGF-beta signaling is activated in periodontitis-affected gingiva, along with enhanced collagen degradation, that is reversed by TGF-beta inhibition. A novel three-dimensional (3D) gel-culture system consisting of primary human gingival fibroblasts (GF) and gingival epithelial (GE) cells in collagen gels was applied. GF populations from patients with severe periodontitis degraded collagen gels, which was reduced by TGF-beta-receptor kinase inhibition. Up-regulation of TGF-beta-responsive genes was evident in GF/GE cocultures. Furthermore, the TGF-beta downstream transducer Smad3C was highly phosphorylated in periodontitis-affected gingiva and 3D cultures. These results imply that TGF-beta signaling is involved in fibroblast-epithelial cell interaction in periodontitis, and suggest that the 3D culture system is a useful in vitro model for therapeutic drug screening for periodontitis.