Endothelial Cells Express Activin A which may serve as an antagonist to TGFβ binding to Activin‐Like Kinase 1 Receptor

Abstract

Transforming growth factor (TGFβ) family and their receptors have been shown to be involved in angiogenesis as well as tumor cells. Members of the family that have been reported to act on endothelial cells are TGFβ, Bone Morphogenetic protein 9 and 10 (BMP‐9, BMP‐10), and Activin A. They all can signal through the type I receptor Activin‐Like Kinase 1 (ALK‐1). We have screened endothelial cells vs tumor cells for ALK‐1, Endoglin, and potential ligands BMP‐10 and Activin A to determine which ligands and receptors may be active in signaling in angiogenesis. We show that endothelial cells express ALK‐1 and endoglin as well as BMP‐10 and Activin A by quantitative RT‐PCR. Transfecting Human Umbilical Vein Endothelial Cells (HUVEC) compared to human 293 cells and Hela cells with an ALK‐1 plasmid resulted in increased expression of ALK‐1 in all cell lines. ALK‐1 overexpression did not affect Smad 1 or Smad 5 expression but increased BMP‐10 and Activin A expression in HUVEC. This data suggests these factors may function as endogenous ligands to control endothelial function and angiogenesis. TGFβ can only bind ALK‐1 on endothelial cells at 37°C but not 23 or 4° C. But our results indicate that endogenous Activin A is bound to ALK‐1 and can be displaced by added TGFβ. This supports the finding above that HUVEC express Activin A. Thus Activin A may function as an endogenous regulator of TGFβ function in endothelial cells.Support or Funding InformationResearch support was from an SFSC Innovation Grant (MP), Portz National Honors Fellowships (GW and NM), and funds from Saint Leo University (ID).