cAMP inhibits TGFbeta1-induced in vitro angiogenesis

FEBS Letters
Beatriz del Valle-PérezFrancesc Viñals

Abstract

Transforming growth factor-beta (TGFbeta1) is a proangiogenic factor both, in vitro and in vivo, that is mainly involved in the later phases of angiogenesis. In an attempt to identify genes that participate in this effect, we found that TGFbeta1 down-regulates expression of adenylate cyclase VI. In addition, cAMP analogs (8-Bromo-cAMP) and forskolin (an adenylate cyclase activator) also reduced TGFbeta1-induced in vitro angiogenesis in mouse endothelial cell lines and in primary cultures of human umbilical vein endothelial cells on collagen gels. Induction of Ets-1 and plasminogen activator inhibitor-1 (PAI-1) by TGFbeta1 was blocked by these cAMP agonists and activators, in the absence of effects on endothelial cell viability. Moreover, the signal transduction pathways stimulated by TGFbeta1 were unaffected. Thus, Smad2 was normally phosphorylated and translocated to the nucleus in the presence of forskolin. In contrast, transfection studies using the PAI-1-promoter indicated that these cAMP analogues inhibit transcriptional stimulation by TGFbeta1. Electrophoretic mobility shift assay showed that Smad2/3 were bound normally to a TGFbeta1-response region in the presence of the cAMP analogs. In all, these data suggest that the ...Continue Reading

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Citations

Jun 1, 2005·Pharmacology & Therapeutics·María Jesús SanzEsteban J Morcillo
Sep 8, 2010·Biochemical and Biophysical Research Communications·Zhongcai MaDavid Paek
Aug 10, 2006·American Journal of Physiology. Renal Physiology·Giovanna GiannicoJerry Yee
May 28, 2019·Life Sciences·Ankita Mehta, Bhoomika M Patel

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