Modulation of transcriptional activity of collagen genes for the treatment of fibrotic diseases

Abstract

It is now evident that the persistent overproduction of collagen is responsible for the progressive nature of tissue fibrosis in a variety of diseases, collectively known as fibrotic diseases. Upregulation of collagen gene expression in fibroblasts appears to be a critical event in their pathogenesis. This process appears to be due, in most cases, to increased transcriptional activity of the genes encoding various collagens and other extracellular matrix proteins. The transcriptional activation of collagen genes suggests a fundamental alteration in the regulatory control of their expression. Trans-acting nuclear factors that bind to cis-acting elements in promoter and enhancer (intronic) regions of collagen genes modulate their basal and inducible transcriptional activity. It is highly likely that transcriptional factors are also crucial components of the pathologic process that leads to tissue fibrosis. The identification of transcription factors involved in the regulation of normal collagen gene expression and the elucidation of their precise role in the abnormal collagen gene expression characteristic of fibrotic diseases may provide effective approaches to the therapy of these incurable and often progressive diseases. Indeed, several new potential therapeutic agents for the fibrotic diseases focus on the modification of the transcriptional activity of collagen genes as a promising target. The patents covering these agents will be reviewed here.

• collagen genes
• fibrosis
• fibrotic diseases
• systemic sclerosis
• transcription factors
• Type I collagen