Complex epithelial-mesenchymal interactions modulate transforming growth factor-β expression in keloid-derived cells
Complex epithelial-mesenchymal interactions modulate transforming growth factor-β expression in keloid-derived cells
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DOI：
10.1111/j.1067-1927.2004.012507.x
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发表时间：
2004-09-01
影响因子：
2.9
通讯作者：
Yang, GP
中科院分区：
文献类型：
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作者：
Xia, W;Phan, TT;Yang, GP
瘢痕疙瘩是代表病理性伤口愈合反应的增生性皮肤生长。我们先前已经证明，与正常角质形成细胞相比，瘢痕疙瘩或正常皮肤来源的成纤维细胞与瘢痕疙瘩来源的角质形成细胞共培养时具有升高的增殖率。在这些研究中，我们使用双室共培养系统研究了转化生长因子-β（TGF-β）对这种现象的贡献。在加入泛TGF-β中和抗体的情况下，共培养中的成纤维细胞增殖较慢。瘢痕疙瘩角质形成细胞在共培养表达更多的TGF-β 1，-β 3，和TGF-β受体1比正常角质形成细胞。与瘢痕疙瘩角质形成细胞共培养的瘢痕疙瘩成纤维细胞表达更多的TGF-β 1、TGF-β 2、TGF-β受体1和Smad 2的mRNA。与正常角质形成细胞相比，瘢痕疙瘩成纤维细胞与瘢痕疙瘩角质形成细胞共培养时也产生更多的I型胶原、结缔组织生长因子和胰岛素样生长因子-II/甘露糖-6-磷酸受体。当成纤维细胞与角质形成细胞共培养时，总的和活化的TGF-β活性水平增加，与TGF-β转录活性的变化相关。总之，我们发现一个复杂的旁分泌相互作用调节TGF-β mRNA的表达和激活角质形成细胞和成纤维细胞之间。这些数据表明，瘢痕疙瘩发病机制可能是由于瘢痕疙瘩角质形成细胞增加的TGF-β产生和活化，以及瘢痕疙瘩成纤维细胞中升高的TGF-β表达、利用和信号传导。
Keloids are proliferative dermal growths representing a pathologic wound healing response. We have previously demonstrated that coculture of fibroblasts derived from either keloid or normal skin have an elevated proliferation rate when cocultured with keloid-derived keratinocytes vs. normal keratinocytes. In these studies, we examined the contribution of transforming growth factor-beta (TGF-beta) to this phenomenon using a two-chamber coculture system. Fibroblast proliferation in coculture was slower with the addition of a pan-TGF-beta neutralizing antibody. Keloid keratinocytes in coculture expressed more TGF-beta1, -beta3, and TGF-beta receptor 1 than normal keratinocytes. Keloid fibroblasts cocultured with keloid keratinocytes expressed more mRNA for TGF-beta1, -beta2, TGF-beta receptor 1, and Smad2. Keloid fibroblasts also produced more type I collagen, connective tissue growth factor, and insulin-like growth factor-II/mannose-6-phosphate receptor when cocultured with keloid keratinocytes vs. normal keratinocytes. Levels of total and activated TGF-beta activity increased when fibroblasts were cocultured with keratinocytes, correlating with the changes in transcriptional activity of TGF-beta. In conclusion, we find a complex paracrine interaction regulates TGF-beta mRNA expression and activation between keratinocytes and fibroblasts. These data suggest that keloid pathogenesis may result from both an increased TGF-beta production and activation by the keloid keratinocyte, and elevated TGF-beta expression, utilization, and signaling in keloid fibroblasts.