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Institute
- Biowissenschaften (92) (remove)
The project focuses on the efficiency of combined technologies to reduce the release of micropollutants and bacteria into surface waters via sewage treatment plants of different size and via stormwater overflow basins of different types. As a model river in a highly populated catchment area, the river Schussen and, as a control, the river Argen, two tributaries of Lake Constance, Southern Germany, are under investigation in this project. The efficiency of the different cleaning technologies is monitored by a wide range of exposure and effect analyses including chemical and microbiological techniques as well as effect studies ranging from molecules to communities.
Angiogenesis, the formation of new blood vessels from existing ones, is a fundamental biological process required for embryonic development; it also plays an important role during postnatal organ development and various physiological and pathological remodeling processes in the adult organism. Vascular endothelial growth factor (VEGF) and its main receptor, VEGF receptor-2 (VEGFR-2), play a central role in angiogenesis. VEGFR-2 expression is strongly upregulated in angiogenic vessels, but the mechanisms regulating VEGFR-2 expression are not well understood. We found in this study that the G-protein α subunit Gα13 plays an important role in the regulation of VEGFR-2 expression. In vitro, we found that knockdown of Gα13 reduced VEGFR-2 expression in human umbilical vein endothelial cells and impaired responsiveness to VEGF-A. This phenotype was rescued by adenoviral normalization of VEGFR-2 expression. Gα13-dependent VEGFR-2 expression involved activation of the small GTPase RhoA and transcription factor NF-κB; it was abrogated by deletion of the NF-κB binding site at position -84 of the VEGFR-2 promoter. In vivo, endothelial cell-specific loss of Gα13 resulted in reduced VEGFR-2 expression, impaired responsiveness towards VEGF-A in Matrigel assays, and reduced retinal angiogenesis. Importantly, also tumor vascularization was diminished in the absence of endothelial Gα13, resulting in reduced tumor growth. Taken together, we identified Gα13-dependent NF-κB activation as a new pathway underlying the transcriptional regulation of VEGFR-2 during retinal and tumor angiogenesis.