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Original Articles
Hypothesis: Thalidomide embryopathy—proposed mechanism of action
Article first published online: 7 FEB 2000
DOI: 10.1002/(SICI)1096-9926(200003)61:3<189::AID-TERA6>3.0.CO;2-W
Copyright © 2000 Wiley-Liss, Inc.
1096-9926/asset/cover.gif?v=1&s=05db30b65433a361fec6715625325343a1f06765 "Teratology")
Additional Information
How to Cite
Stephens, T. D. and Fillmore, B. J. (2000), Hypothesis: Thalidomide embryopathy—proposed mechanism of action. Teratology, 61: 189–195. doi: 10.1002/(SICI)1096-9926(200003)61:3<189::AID-TERA6>3.0.CO;2-W
Publication History
- Issue published online: 7 FEB 2000
- Article first published online: 7 FEB 2000
- Manuscript Accepted: 7 SEP 1999
- Manuscript Received: 8 MAR 1999
- Abstract
- References
- Cited By
Abstract
We propose that thalidomide affects the following pathway during limb development: Growth factors (FGF-2 and IGF-I) attach to receptors on limb bud mesenchymal cells and initiate some second messenger system (perhaps SP-1), which activates αv and β3 integrin subunit genes. The resulting αv β3 integrin proteins stimulate angiogenesis in the developing limb bud. Several steps in this pathway depend on the activation of genes with primarily GC promoters (GGGCGG). Thalidomide, or a hydrolysis or metabolic breakdown product, specifically binds to GC promoter sites and inhibits the transcription of those genes. Inhibition of the genes interferes with normal angiogenesis, which results in truncation of the limb. Teratology 61:189–195, 2000. © 2000 Wiley-Liss, Inc.