Role of transcription factors in angiogenesis: Ets-1 promotes angiogenesis as well as endothelial apoptosis

Abstract

Angiogenesis is a complex phenomenon that requires at least migration, proliferation, and tubular morphogenesis of endothelial cells (ECs). Some genes are expressed in ECs during these processes, and therefore the regulation of gene expression in ECs is critical. Increasing evidence suggests that the Ets family of transcription factors plays an important role in angiogenesis. We observed that Ets-1, a prototype of the Ets family of transcription factors, promoted angiogenesis by inducing the expression of matrix metalloproteinases and integrin beta3 in ECs, and the elimination of the transactivation activity of Ets-1 by a dominant negative molecule inhibited angiogenesis. Apoptosis, a term used to describe the terminal morphological and biochemical events seen in programmed cell death, is critical for the development or reconstitution of multicellular organs. Apoptosis of ECs is observed at the initiation of angiogenesis, at the branching or communication with newly formed vessels, and at the regression of neo-vessels. The Ets family of transcription factors is generally thought to be anti-apoptotic. However, there are conflicting reports on the role of Ets-1 in apoptosis. We examined the role of Ets-1 in apoptosis of ECs and found that Ets-1 was pro-apoptotic to ECs by modulating the expression of several apoptosis-related genes.