We have investigated human neonatal fibroblast synthetic activity in response to fibrin substrates and components of fibrin formation and degradation. Greater than threefold downregulation of procollagen mRNA levels was seen 24 hours after fibroblasts were grown on fibrin gels as compared to tissue
Low oxygen tension increases mRNA levels of alpha 1 (I) procollagen in human dermal fibroblasts
โ Scribed by Vincent Falanga; Theresa A. Martin; Hajime Takagi; Robert S. Kirsner; Todd Helfman; Jeffrey Pardes; M. Sofia Ochoa
- Publisher
- John Wiley and Sons
- Year
- 1993
- Tongue
- English
- Weight
- 566 KB
- Volume
- 157
- Category
- Article
- ISSN
- 0021-9541
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โฆ Synopsis
Dermal fibroblasts exposed to low oxygen tension show upregulated synthesis of transforming growth factor-beta 1 (TGF-beta 11, an established stimulatory peptide in the formation of extracellular matrix proteins. In this report, procollagen synthesis was measured in cultures of confluent adult human dermal fibroblasts exposed to either standard (20%) or low (2%) oxygen tension. By Northern blot analysis the steady state levels of alpha 1 (I) procollagen mRNA were increased by 75 to 150% of control (standard oxygen) as early as 12 hours and more than 200% 96 hours after exposure of cells to low oxygen. Similar increases in procollagen mRNA levels were obtained in hypoxic fibroblast cultures in a collagen lattice. The stimulatory effect of hypoxia on procollagen mRNA levels in fibroblast monolayers was diminished by antibodies to TGF-beta, and could not be augmented further by the addition of TGF-beta 1 , evidence that hypoxic fibroblasts may already be maximally stimulated by TGF-beta 1 . We conclude that low oxygen tension enhances steady state mRNA levels of alpha 1 (I) procollagen, and that this effect is mediated at least in part by TGF-beta 1 .
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