Oligodeoxynucleotide decoy therapy blocks type 1 procollagen transcription and the prolyl hydroxylase β subunit translation

Abstract

Persistent transforming growth factor-β1 (TGF-β1) exposure to lungs increases type 1 collagen synthesis and deposition resulting in excess fibrosis which leads to morbidity and possibly death. We now report using human embryonic lung fibroblasts in the presence of TGF-β1, a novel double-stranded (ds) DNA decoy with phosphorothioate (PT) linkages, containing the TGF-β cis-element found in the distal promoter region of the COL1A1 gene which silences COL1A1 gene expression. In a cell-free protein translation system, we have previously reported that collagen synthesis was inhibited by disulfide isomerase, the prolyl-4-hydroxylase (P-4-H) β subunit. By comparative proteomics dsdecoy therapy increased the levels of disulfide isomerase, the P-4-H β subunit. These findings taken together support the notion that the dsdecoy inhibits type 1 collagen synthesis at both the transcriptional and translational levels. © 2007 Wiley-Liss, Inc.