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

Full Abstract

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.

Author information

Author/s: Lok, Chun-Nam (CN); Ehrlich, H Paul (HP); White, Sheryl L (SL); Buttolph, Thomas R (TR); Cutroneo, Kenneth R (KR); Chiu, Jen-Fu (JF);

Affiliation: Department of Anatomy, Hong Kong University, Peoples' Republic of China.

Grants: P20RR16435 (Agency:NCRR NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Journal of cellular biochemistry (J Cell Biochem), published in United States. (Language: eng)

Reference: 2008-Mar; vol 103 (issue 4) : pp 1066-75

Dates: Created 2008/02/25; Completed 2008/06/20; Revised 2008/11/21;

PMID: 18027883, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Cell Line
Collagen Type I - biosynthesis; genetics
Embryo, Mammalian - cytology
Fibroblasts - metabolism
Humans
Lung - cytology
Oligonucleotides - genetics; pharmacology

Associated Chemicals: Collagen Type I (0) ; Oligonucleotides (0) ; Oligonucleotides, Antisense (0) ; Transforming Growth Factor beta1 (0) ; collagen type I, alpha 1 chain (0) ; Procollagen-Proline Dioxygenase (EC 1.14.11.2)

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