Transgenic Expression of Transforming Growth Factor Beta 1 (TGF–B1) Blocks Maturation of Retinal Blood Vessels by Disruption of Tie2 Signaling

Abstract

Abstract: : Purpose: Transforming growth factor beta 1 (TGF–ß1) is necessary for the differentiation of stable blood vessels. Tie2 expression in endothelial cells is also necessary for development of stable blood vessels. We have found that transgenic expression of TGF–ß1 disrupts establishments of stable blood vessels in the retina. The purpose of this study is to determine the mechanism by which TGF–ß1 is interfering in vascular growth and differentiation. Methods: We have used real–time PCR, western blots, and immunohistochemistry to measure Tie2 expression in retinal vasculature. Results: TGF–ß1 transgenic mice exhibit lower levels of Tie2 expression when compared to non–transgenic mice. Our immunohistochemistry analyses have confirmed that Tie2 expression in vascular endothelial cells is reduced in transgenic mice expressing TGF–ß1. Conclusions: There is a significant difference in Tie2 expression in TGF–ß1 transgenic mice. Our results suggest that TGF–ß1 is a regulator of Tie2 signaling. Since Tie2 signaling is important for establishment and maintenance of the blood retinal barrier, our results suggest that hyper–activation of TGF–ß1 in diabetic patients may be a contributing factor in diabetic vascular breakdown.

Keywords: growth factors/growth factor receptors • diabetic retinopathy • transgenics/knock-outs