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丰富的蛋白质，由两条α1（I）链和一条α 2（I）链组成，它们协调表达。ColF 1是一种DNA结合蛋白，它特异性地结合于α2（I）胶原基因启动子上游-400bp处，在体外激活α2（I）胶原基因的转录，由两个多肽组成。本实验对α2（I）胶原基因转录因子的cDNA克隆进行了研究。42 kDa多肽与Pur α相同，Pur α是一种与人c-mye基因上游区结合的核蛋白; 40 kDa多肽与Pur β相同，已部分测序，与Pur α有很强的同源性。测定了Pur β cDNA的全长序列。我们一直在寻找表达异常胶原蛋白水平的成纤维细胞作为体内I型胶原基因转录调控机制的模型系统。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。

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.