Oligodeoxynucleotide decoy therapy blocks type 1 procollagen transcription and the prolyl hydroxylase beta subunit translation.
Persistent transforming growth factor-beta1 (TGF-beta1) 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-beta1, a novel double-stranded (ds) DNA decoy with phosphorothioate (PT) linkages, containing the TGF-beta 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) beta subunit. By comparative proteomics dsdecoy therapy increased the levels of disulfide isomerase, the P-4-H beta subunit. These findings taken together support the notion that the dsdecoy inhibits type 1 collagen synthesis at both the transcriptional and translational levels.
Lok
Chun-Nam
CN
Department of Anatomy, Hong Kong University, Peoples' Republic of China.
Ehrlich
H Paul
HP
White
Sheryl L
SL
Buttolph
Thomas R
TR
Cutroneo
Kenneth R
KR
Chiu
Jen-Fu
JF
D002460:Cell Line; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology; D009841:Oligonucleotides / Q000235:genetics / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D011393:Procollagen-Proline Dioxygenase / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D014158:Transcription, Genetic; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000494:pharmacology
D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D053773:Transforming Growth Factor beta1; D011393:Procollagen-Proline Dioxygenase