ACTIVATION OF COLLAGEN GENE-EXPRESSION IN KELOIDS - COLOCALIZATION OF TYPE-I AND TYPE-VI COLLAGEN AND TRANSFORMING GROWTH FACTOR-BETA-1 MESSENGER-RNA
ACTIVATION OF COLLAGEN GENE-EXPRESSION IN KELOIDS - COLOCALIZATION OF TYPE-I AND TYPE-VI COLLAGEN AND TRANSFORMING GROWTH FACTOR-BETA-1 MESSENGER-RNA
复制标题
DOI：
10.1111/1523-1747.ep12480289
复制
发表时间：
1991-08-01
影响因子：
6.5
通讯作者：
UITTO, J
中科院分区：
文献类型：
--
作者：
PELTONEN, J;HSIAO, LL;UITTO, J
以未经治疗、临床活动的瘢痕疙瘩为模型系统，研究细胞外基质和转化生长因子-β1基因在纤维性皮肤病中的空间表达。原位杂交将I型和VI型胶原基因的活跃表达定位于含有大量成纤维细胞的区域，并明显代表病变的扩张边界。在这个区域内，微血管内皮细胞也表达I型胶原基因，通过同时使用胶原蛋白基因表达的原位杂交和第VIII因子相关抗原的免疫定位来评价，第八因子相关抗原是内皮细胞分化的标志。与III型胶原基因的表达相比，I型和VI型胶原基因的表达有选择性地增强。在I型和VI型胶原基因表达活跃的区域也检测到了转化生长因子-β1的蛋白和mRNA，表明转化生长因子-β1基因被转录，相应的蛋白沉积在胶原基因表达升高的区域，包括微血管内皮细胞。我们的结论是，瘢痕疙瘩纤维化反应的最初步骤涉及新生血管内皮细胞表达转化生长因子-β1基因，从而激活相邻成纤维细胞表达显著升高的转化生长因子-β1以及I型和VI型胶原基因。
Untreated, clinically active keloids were examined as a model system to study the spatial expression of extracellular matrix and transforming growth factor-beta-1 (TGF-beta-1) genes in fibrotic skin diseases. In situ hybridizations localized active expression of type I and VI collagen genes to the areas containing an abundance of fibroblasts and apparently representing the expanding border of the lesions. Within this zone, microvascular endothelial cells also expressed the type I collagen genes, as evaluated by simultaneous use of in situ hybridization for collagen gene expression and immunolocalization for factor VIII-related antigen, a marker for endothelial cell differentiation. Slot-blot hybridizations of RNA isolated from this zone suggested that the expression of type I and VI collagen genes was selectively enhanced, as compared to type III collagen gene expression. TGF-beta-1 protein and mRNA were also detected in areas active in type I and type VI collagen gene expression, indicating that TGF-beta-1 gene is transcribed and the corresponding protein is deposited in areas of elevated collagen gene expression, including microvascular endothelial cells. We conclude that the initial step in the development of fibrotic reaction in keloids involves the expression of the TGF-beta-1 gene by the neovascular endothelial cells, thus activating the adjacent fibroblasts to express markedly elevated levels of TGF-beta-1, as well as type I and VI collagen genes.