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CD105 antagonizes the inhibitory signaling of transforming growth factor beta1 on human vascular endothelial cells
1Department of Pathological Sciences, Medical School, University of Manchester, Manchester M13 9PT, U.K.
Abstract:
CD105 (endoglin), a receptor for transforming growth factor beta (TGFbeta), is highly expressed in tissue-cultured, activated endothelial cells in vitro and in tissues undergoing angiogenesis in vivo. The absence of CD105 in knockout mice leads to their death from defective vascular development, but the role of CD105 in the modulation of angiogenesis has not been elucidated. TGFbeta1 is a well-recognized regulator of angiogenesis. Using an antisense approach, we have shown that inhibition of CD105 protein translation in cultured human endothelial cells enhances the ability of TGFbeta1 to suppress growth and migration in these cells. The ability of endothelial cells to form capillary tubes was evaluated by the use of a 3-dimensional collagen matrix system where TGFbeta1 not only reduced the length of capillary-like structures, but also caused massive mortality in CD105-deficient cells compared to control cultures. These results provide direct evidence that CD105 antagonizes the inhibitory effects of TGFbeta1 on human vascular endothelial cells and that normal cellular levels of CD105 are required for the formation of new blood vessels.
Insights
CD105 (endoglin) antagonizes TGFbeta1's inhibitory effects on human vascular endothelial cells. Normal CD105 levels are essential for new blood vessel formation, crucial for angiogenesis.
Area of Science:
- Cell Biology
- Vascular Biology
- Biochemistry
Background:
- CD105 (endoglin) is a transforming growth factor beta (TGFbeta) receptor highly expressed in activated endothelial cells and during angiogenesis.
- While CD105 knockout mice exhibit lethal vascular development defects, its precise role in modulating angiogenesis remains unclear.
- Transforming growth factor beta 1 (TGFbeta1) is a known regulator of angiogenesis.
Purpose of the Study:
- To investigate the role of CD105 in the modulation of angiogenesis.
- To elucidate how CD105 influences the effects of TGFbeta1 on endothelial cells.
- To determine the necessity of normal CD105 levels for new blood vessel formation.
Main Methods:
- Utilized an antisense approach to inhibit CD105 protein translation in cultured human endothelial cells.
- Assessed endothelial cell growth and migration.
- Evaluated capillary tube formation using a 3-dimensional collagen matrix system.
Main Results:
- Inhibition of CD105 protein translation enhanced TGFbeta1's suppressive effects on endothelial cell growth and migration.
- TGFbeta1 significantly reduced capillary-like structure length and increased mortality in CD105-deficient cells within a 3D collagen matrix.
- CD105 was shown to antagonize the inhibitory actions of TGFbeta1 on human vascular endothelial cells.
Conclusions:
- CD105 plays a critical role in antagonizing the inhibitory effects of TGFbeta1 on human vascular endothelial cells.
- Normal cellular levels of CD105 are indispensable for the formation of new blood vessels (angiogenesis).
- These findings highlight CD105 as a key mediator in vascular development and angiogenesis regulation.