LOW-OXYGEN TENSION INCREASES MESSENGER-RNA LEVELS OF ALPHA-1 (I) PROCOLLAGEN IN HUMAN DERMAL FIBROBLASTS

Dermal fibroblasts exposed to low oxygen tension show upregulated synt hesis of transforming growth factor-beta 1 (TGF-beta 1), an establishe d stimulatory peptide in the formation of extracellular matrix protein s. In this report, procollagen synthesis was measured in cultures of c onfluent adult human dermal fibroblasts exposed to either standard (20 %) or low (2%) oxygen tension. By Northern blot analysis the steady st ate 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 i n 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-be ta 1, evidence that hypoxic fibroblasts may already be maximally stimu lated by TGF-beta 1. We conclude that low oxygen tension enhances stea dy state mRNA levels of alpha 1 (I) procollagen, and that this effect is mediated at least in part by TGF-beta 1. (C) 1993 Wiley-Liss, Inc.