Regulation of type I collagen genes expression

Type I collagen is the major component of many extracellular matrices, and its accumulation characterizes most fibrotic processes. It is synthesized b y a small number of discrete cell types, including fibroblasts, osteoblasts and odontoblasts. Analysis of transgenic mice harbouring different segment s of the promoters of the mouse pro-alpha1(I) and pro-alpha2(I) genes has l ed to the conclusion that this tissue-specific expression is controlled by different cis-acting elements which are responsible for the expression of t ype I collagen genes in different type I collagen-producing cells. Transact ing factors which bind to these different tissue-specific elements are stil l unknown, but they probably act by modifying the chromatin structure. In f ibroblastic cells, various soluble molecules can modulate the transcription of type I collagen genes. Analysis of the pro-alpha1(I) and pro-alpha2(I) proximal promoters has led to the identification of different cis-acting el ements which can modulate the expression of reporter genes, in transfection experiments. Among these cis-acting elements, a sequence located between - 378 and -183 bp in the human pro-alpha2(I) promoter appears to mediate the transcriptional effects of transforming growth factor-beta. It binds a larg e multimeric complex which contains Sp1, as well as AP1 and other DNA-bindi ng proteins which have not yet been identified.