Blocking Sp1 transcription factor broadly inhibits extracellular matrix gene expression in vitro and in vivo: implications for the treatment of tissue fibrosis

摘要

Sp1 is a transcription factor that is involved in the basal expression of ECM genes and is therefore important in fibrotic processes. The present invention relates to methods wherein transcriptional repression of the Sp1 gene by antisense Sp1 is used to reduce the expression of several ECM genes, without significant alteration in cell growth. The present invention further relates to decoy Sp1 binding oligonucleotides that interfere with Sp1 binding to its target DNA, thereby inhibiting ECM gene promoter activity both in vitro and in vivo. Targeting Sp1 will therefore allow for the efficient inhibition of ECM gene expression, and thereby allow for an alternative, non-toxic, therapeutic approach in the treatment of fibrotic disorders.