TRANSCRIPTION AND EXPRESSION OF TRANSFORMING GROWTH-FACTOR TYPE-BETA IN THE SKIN OF PROGRESSIVE SYSTEMIC-SCLEROSIS - A MEDIATOR OF FIBROSIS
TRANSCRIPTION AND EXPRESSION OF TRANSFORMING GROWTH-FACTOR TYPE-BETA IN THE SKIN OF PROGRESSIVE SYSTEMIC-SCLEROSIS - A MEDIATOR OF FIBROSIS
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DOI：
10.1111/1523-1747.ep12874503
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发表时间：
1990-02-01
影响因子：
6.5
通讯作者：
WICK, G
中科院分区：
文献类型：
--
作者：
GRUSCHWITZ, M;MULLER, PU;WICK, G
进行性系统性硬化症的特征在于广泛的全身性纤维化破坏，其与皮肤和其他受累器官中胶原蛋白和其他细胞外大分子的积累增加相关。已经表明，从单核细胞或内皮细胞释放的介质在结缔组织代谢的初始激活中起关键作用。转化生长因子β（TFG-β 1、TGF-β 2）介导上皮细胞增殖的抑制以及纤连蛋白和胶原蛋白基因表达的诱导。因此，我们通过原位杂交和免疫组织化学研究了PSS皮肤中TGF-β 1和TGF-β 2 mRNA和最终蛋白质的分布，并与其他炎性皮肤病和健康对照进行了比较。我们的研究揭示了在急性和慢性PSS中，以及在其它炎性皮肤病中，真皮和皮下浸润细胞中的TGF-β 1和TGF-β 2 mRNA。在该浸润物附近，单个TGF-β急性期PSS可见阳性成纤维细胞。所有皮肤附件的上皮细胞胞浆均显示TGF-β。转录本和没有明显的差异，在患病和健康的皮肤样品之间的放射自显影颗粒的分布和数量。特别地，我们可以证明TGF-β 1/2在外根鞘的上皮毛囊细胞中的丰富表达。通常，TGF-β 2的表达比TGF-β 1的表达丰度低。 免疫组织化学研究显示了相同的分布模式的最终蛋白质。我们的数据表明TGF-β.在浸润细胞中的表达不是纤维化疾病的特异性特征，但似乎通常与高度增殖的细胞有关，可能在调节细胞生理学中起共同的介体作用，对于细胞生长的负控制特别重要。
Progressive systemic sclerosis is characterized by extensive generalized fibrotic destruction associated with increased accumulation of collagen and other extracellular macromolecules in the skin and other involved organs. It has been suggested that mediators released from mononuclear or endothelial cells play a critical role in the initial activation of connective tissue metabolism. Transforming growth factors .beta.(TFG-.beta.1, TGF-.beta.2) mediate the inhibition of epithelial cell proliferation and the induction of fibronectin and collagen gene expression. Therefore, we investigated the distribution of both TGF-.beta.1 and TGF-.beta.2 mRNA and the final proteins in PSS skin in comparison with other inflammatory dermatoses and healthy controls by means of in situ hybridization and immunohistochemistry. Our studies revealed TGF-.beta.1 and -.beta.2 mRNA in dermal and subcutaneous infiltrating cells in both acute and chronic PSS, but also in the other inflammatory skin disorders. In the vicinity of this infiltrate single TGF-.beta. positive fibroblasts could be found in acute PSS. The cytoplasm of epithelial cells of all skin adnexa showed TGF-.beta. transcripts and no apparent differences were seen in the distribution and number of autoradiographic grains between diseased and healthy skin samples. Especially, we could demonstrate abundant expression of TGF-.beta.1/2 in epithelial hair follicle cells of the outer root sheath. Generally, the expression of TGF-.beta.2 was less abundant than TGF-.beta.1. Immunohistochemical studies revealed the same distribution pattern of the final proteins. Our data indicate that TGF-.beta. expression in infiltrating cells is not a specific feature of fibrotic disease, but seems to be associated with highly proliferating cells in general, perhaps functioning as common mediator in regulation of cellular physiology with special importance for negative control of cell growth.