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Low oxygen tension decreases receptor binding of peptide growth factors in dermal fibroblast cultures
V Falanga1, H Takagi, P I Ceballos
1University of Miami School of Medicine, Department of Dermatology and Cutaneous Surgery, Florida 33136.
Abstract:
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.
Insights
Low oxygen levels significantly reduce the binding and number of receptor sites for epidermal growth factor (EGF) and transforming growth factor-beta 1 (TGF-beta) in human fibroblasts. These effects are reversible when oxygen levels are restored.
Area of Science:
- Cell Biology
- Molecular Biology
- Physiology
Background:
- Epidermal Growth Factor (EGF) and Transforming Growth Factor-beta 1 (TGF-beta) are crucial signaling molecules.
- Cellular responses to oxygen tension are vital in various physiological and pathological processes.
Purpose of the Study:
- To investigate the impact of low oxygen tension (hypoxia) on EGF and TGF-beta receptor binding in human dermal fibroblasts.
- To determine the effect of hypoxia on the number of available receptor binding sites for these growth factors.
Main Methods:
- Human dermal fibroblasts were cultured under low (2%) and standard (20%) oxygen tensions.
- Receptor binding assays were performed using radiolabeled 125I-TGF-beta and 125I-EGF.
- Northern analysis was used to assess TGF-beta type II receptor mRNA levels.
Main Results:
- Low oxygen tension significantly decreased the binding of both 125I-TGF-beta (65%) and 125I-EGF (62%) compared to standard oxygen (P < 0.02).
- Hypoxia reduced the number of binding sites for EGF (44%) and TGF-beta (33%).
- Diminished TGF-beta receptor binding in hypoxia correlated with a 10-fold decrease in TGF-beta type II receptor mRNA levels.
Conclusions:
- Low oxygen tension impairs EGF and TGF-beta receptor binding in human dermal fibroblasts.
- Hypoxia reduces the synthesis of TGF-beta receptors, indicated by decreased mRNA levels.
- These findings suggest that oxygen levels play a critical role in regulating growth factor signaling pathways.