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Bradykinin-induced growth inhibition of normal rat kidney (NRK) cells is paralleled by a decrease in
E J Van Zoelen1, P H Peters, G B Afink
1Department of Cell Biology, University of Nijmegen, Faculty of Science, The Netherlands.
Abstract:
Normal rat kidney fibroblasts, grown to density arrest in the presence of epidermal growth factor (EGF), can be induced to undergo phenotypic transformation by treatment with transforming growth factor beta or retinoic acid. Here we show that bradykinin blocks this growth-stimulus-induced loss of density-dependent growth arrest by a specific receptor-mediated mechanism. The effects of bradykinin are specific, and are not mimicked by other phosphoinositide-mobilizing agents such as prostaglandin F2 alpha. Northern-blot analysis and receptor-binding studies demonstrate that bradykinin also inhibits the retinoic acid-induced increase in EGF receptor levels in these cells. These studies provide additional evidence that EGF receptor levels modulate EGF-induced expression of the transformed phenotype in these cells.
Insights
Bradykinin prevents growth factor-induced loss of cell cycle arrest in fibroblasts. This receptor-mediated mechanism specifically blocks transforming growth factor beta and retinoic acid effects, impacting epidermal growth factor receptor levels.
Area of Science:
- Cell biology
- Molecular endocrinology
- Cancer research
Background:
- Normal rat kidney fibroblasts exhibit density-dependent growth arrest.
- Epidermal growth factor (EGF) is present during this arrest.
- Phenotypic transformation can be induced by transforming growth factor beta (TGF-β) or retinoic acid (RA).
Purpose of the Study:
- To investigate the effect of bradykinin on growth stimulus-induced loss of density-dependent growth arrest.
- To determine the mechanism of bradykinin's action.
- To examine bradykinin's effect on epidermal growth factor (EGF) receptor levels.
Main Methods:
- Treatment of density-arrested rat kidney fibroblasts with bradykinin, TGF-β, RA, and prostaglandin F2 alpha.
- Northern-blot analysis to assess gene expression.
- Receptor-binding studies to quantify receptor levels.
Main Results:
- Bradykinin specifically blocks the loss of density-dependent growth arrest induced by TGF-β or RA.
- Bradykinin's effect is receptor-mediated and not mimicked by prostaglandin F2 alpha.
- Bradykinin inhibits the RA-induced increase in EGF receptor levels.
Conclusions:
- Bradykinin acts via a specific receptor-mediated mechanism to maintain density-dependent growth arrest.
- Bradykinin influences EGF receptor levels, suggesting a role in modulating EGF-induced cell transformation.
- These findings highlight a novel regulatory pathway in fibroblast growth control.