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%) oxygen tension. Compared to standard oxygen, the binding of both 125I-TGF-beta and 125I-EGF in low oxygen tension was diminished by a mean of 65 and 62%, respectively (P < 0.02), and was reversed by reexposure of cultures to standard oxygen tension. Low oxygen tension decreased the number of binding sites of both EGF (mean = 44%) and TGF-beta (mean = 33%). Preincubation of the media in the two different oxygen conditions showed that alterations in the redox potential of the medium was not 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 and TGF-beta receptor binding and synthesis.
Falanga
V
V
University of Miami School of Medicine, Department of Dermatology and Cutaneous Surgery, Florida 33136.
Takagi
H
H
Ceballos
P I
PI
Pardes
J B
JB
D000328:Adult; D015152:Blotting, Northern; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D010100:Oxygen / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D010100:Oxygen