Crucial role of activin a in tubulogenesis of endothelial cells induced by vascular endothelial growth factor.

Abstract:

:The present study was conducted to elucidate the role of activin A in tubulogenesis of vascular endothelial cells. Activin A was produced in bovine aortic endothelial cells (BAEC). These cells also expressed the type I and type II activin receptors. When added to BAEC cultured in a collagen gel, activin A induced capillary formation. Activin A was as potent as vascular endothelial growth factor (VEGF) and markedly enhanced VEGF-induced tubulogenesis. To examine the role of endogenous activin A, we added follistatin, an inhibitor of activin A. Follistatin nearly completely blocked the VEGF-induced tubulogenesis, and the effect of follistatin was reproduced by transfection of the dominant-negative type II activin receptor gene. In BAEC, activin A increased the expression of VEGF and the VEGF receptors, Flt-1 and Flk-1. On the other hand, VEGF increased the production of activin A. Finally, addition of follistatin, which blocks the action of endogenous activin A, reduced the expression of Flt-1 and Flk-1. These results indicate that an autocrine factor activin A amplifies the effect of VEGF by up-regulating VEGF and its receptors. This effect of activin A is critical in the VEGF-induced tubulogenic morphogenesis in BAEC.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Maeshima K,Maeshima A,Hayashi Y,Kishi S,Kojima I

doi

10.1210/en.2004-0213

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

3739-45

issue

8

eissn

0013-7227

issn

1945-7170

pii

en.2004-0213

journal_volume

145

pub_type

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