How do glucocorticoids compare to oligo decoys as inhibitors of collagen synthesis and potential toxicity of these therapeutics?
Article first published online: 24 MAR 2004
Copyright © 2004 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 92, Issue 1, pages 6–15, 1 May 2004
How to Cite
Cutroneo, K. R. and Sterling, K. M. (2004), How do glucocorticoids compare to oligo decoys as inhibitors of collagen synthesis and potential toxicity of these therapeutics?. J. Cell. Biochem., 92: 6–15. doi: 10.1002/jcb.20030
- Issue published online: 12 APR 2004
- Article first published online: 24 MAR 2004
- Manuscript Accepted: 23 DEC 2003
- Manuscript Received: 19 DEC 2003
- TGF-β element;
- TGF-β activator protein complex;
- Type I procollagen;
- Type III procollagen;
- procollagen antibodies;
- propeptide antibodies;
- Proα1 (I) collagen gene transcription;
- sense oligo decoys;
- extracellular matrix (ECM);
- chloramphenacol acetyltransferase (CAT)
This article demonstrates how glucocorticoids decrease collagen synthesis. The parameters used to assess procollagen synthesis in our laboratory will be compared to those used by others. This article will note all the pertinent literature on the molecular mechanisms of this down regulation of procollagen synthesis. For example, what are the effects of glucocorticoids at the levels of transcription and translation of collagen mRNAs? Finally, we will define a molecular mechanism to inhibit Type I collagen synthesis by decreasing the binding of the TGF-β activator protein complex to the TGF-β element in the distal promoter of the proα1 Type I collagen gene, preventing the 2:1 ratio of α1 to α2 chains in the processed Type I collagen molecule. We will next ask “How do sense oligo decoys decrease Type I collagen synthesis at the in vivo and at the cell levels?” In primary fibrotic cell culture, the double-stranded phosphorothioate oligodeoxynucleotide decoys were more effective than their sense single-stranded counterparts. The molecular mechanism for the decrease in Type I collagen synthesis is the same as glucocorticoids, that is by decreasing the binding of the TGF-β activator protein complex to the TGF-β element in the distal promoter of the proα1 Type I collagen gene for the transcription of the proα1 mRNAs. The reason for using sense oligo decoys as anti-fibrotic agents as compared to the anti-fibrotic glucocorticoids, is that presently marketed and FDA approved glucocorticoids have many untoward side effects which the sense oligo decoys do not have. © 2004 Wiley-Liss, Inc.