LOW-OXYGEN TENSION DECREASES RECEPTOR-BINDING OF PEPTIDE GROWTH-FACTORS IN DERMAL FIBROBLAST-CULTURES

We have investigated receptor binding of epidermal growth factor (EGF) and transforming growth factor-beta 1 (TGF-beta) in cultures of human dermal fibroblasts exposed to low (2%, hypoxia) or standard (20%) oxy gen tension. Compared to standard oxygen, the binding of both I-125-TG F-beta and I-125-EGF in low oxygen tension was diminished by a mean of 65 and 62%, respectively (P < 0.02), and was reversed by reexposure o f cultures to standard oxygen tension. Low oxygen tension decreased th e number of binding sites of both EGF (mean = 44%) and TGF-beta (mean = 33%). Preincubation of the media in the two different oxygen conditi ons showed that alterations in the redox potential of the medium was n ot responsible for the changes observed in receptor binding. As shown by Northern analysis, diminished TGF-beta receptor binding in hypoxia was accompanied by up to a 10-fold decrease in mRNA levels of TGF-beta type II receptor. We conclude that low oxygen tension decreases EGF a nd TGF-P receptor binding and synthesis. (C) 1994 Academic Press, Inc.