Analysis of transcriptional control mechanism for the expression of type I collagen gene in fibrotic skin disorders

I型胶原是真皮中含量最多的蛋白，由两条α1(I)链和一条α 2(I)链协调表达组成。ColF1是一种特异性结合α2(I)胶原启动子片段的DNA结合蛋白，位于α2(I)胶原基因转录起始上游-400bp处，在体外激活α2(I)胶原基因的转录，由两种多肽组成。我们对α2(I)胶原基因转录因子的cDNA克隆进行了研究。结果发现，42kDa多肽与Pur α相同，是一个已报道与人类c-mye基因上游区域结合的核蛋白；40kDa多肽与Pur β相同，已部分测序，与Pur α具有较强的同源性。对Pur β cDNA进行全长测序。我们在体内寻找表达异常水平胶原蛋白的成纤维细胞作为I型胶原基因转录控制机制的模型系统。我们发现两株Ehlers-Danlos综合征成纤维细胞产生极低水平的III型胶原蛋白。

Type I collagen, a most abundant protein in the dermis, consists of two α1(I) chain and one α 2(I) chain which are coordinately expressed. ColF1, a DNA binding protein which specifically binds to a segment of the α2(I) collagen promoter at -400bp upstream of the start of transcription, activates transcription of the α2(I) collagen gene in vitro, and consists of two polypeptides. We investigated on the the cDNA cloning of this transcriptional factor of the α2(I) collagen gene. We found that 42kDa polypeptide were identical to Pur α, is a nuclear protein which has been reported to binds to a upstream region of human c-mye gene, and 40kDa polypeptide were identical to Pur β, has been partially sequenced and has regions of strong homology to Pur α. Full length of Pur β cDNA were sequenced. We had looked for fibroblasts express abnormal levels of collagen as model systems of transcriptional control mechanisms of type I collagen gene in vivo. We found two strains of Ehlers-Danlos syndrome fibroblasts which produced extremely low levels of type III collagen.