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

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...

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Bibliographic Details
Published in:Journal of cellular biochemistry 2008-03, Vol.103 (4), p.1066-1075
Main Authors: Lok, Chun-Nam, Ehrlich, H. Paul, White, Sheryl L., Buttolph, Thomas R., Cutroneo, Kenneth R., Chiu, Jen-Fu
Format: Article
Language:English
Subjects:
Cell Line
collagen synthesis
Collagen Type I - biosynthesis
Collagen Type I - genetics
Embryo, Mammalian - cytology
Fibroblasts - metabolism
gene therapy
Humans
Lung - cytology
oligonucleotide decoy
Oligonucleotides - genetics
Oligonucleotides - pharmacology
Oligonucleotides, Antisense - genetics
Oligonucleotides, Antisense - pharmacology
Procollagen-Proline Dioxygenase - biosynthesis
Promoter Regions, Genetic
Protein Biosynthesis
proteomics
Transcription, Genetic
Transforming Growth Factor beta1 - genetics
Transforming Growth Factor beta1 - pharmacology
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Summary: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. J. Cell. Biochem. 103: 1066–1075, 2008. © 2007 Wiley‐Liss, Inc.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.21477