Collagen gene expression

Abstract

Collagens are extracellular matrix proteins that play important structural roles in many tissues and organs. Thirteen types of collagen, the products of 23 genes, have been described. Most of the collagen genes are developmentally regulated; a given tissue or cell type expresses only a subset of the collagen genes. Type I collagen, the most abundant protein in vertebrate connective tissues, is produced by most cells of mesenchymal origin except hyaline cartilage. Each tissue or cell type expresses the type I collagen genes at a characteristic rate. Maintenance of the normal synthetic rate appears to be important for preservation of normal tissue structure and function. Fibrotic lesions are characterized by increased production of type I collagen. The mechanisms that determine both the normal tissue-specific pattern of type I collagen gene expression and the elevated expression in fibrosis are complex. Both transcriptional and post-transcriptional mechanisms have been described, with modulation of mRNA stability being perhaps the most important post-transcriptional mechanism. Several sequences have been identified in the promoters of the type I collagen genes which are required for transcriptional activity; in addition, transcriptional enhances have been identified within the first introns of the genes. Type I collagen gene expression is also regulated both positively and negatively by a variety of exogenous factors, including inflammatory response mediators. The specific combination of such exogenous factors available in a given tissue probably determines the net rate at which the genes are expressed.