The TGF-β family proteins are among the many cytokines that regulate endothelial cell (EC) behaviour. The activation of TGF-β signaling can trigger the conversion of ECs from a cobblestone morphology into a mesenchymal-like cell type with fibroblast appearance, termed endothelial-to-mesenchymal transition (EndMT). EndMT is pivotal for the development of cardiovascular system and also causally links to the occurrence and development of pathological processes in multiple diseases. In this thesis, we elucidated the role of the transcription factors SNAIL and inhibitor of DNA-binding proteins (IDs) in TGF-β/BMP-induced EndMT. What’s more, we synthesized and identified two novel macrocyclic BMPRI inhibitors and assessed their inhibitory effects on ECs function, including homeostatic angiogenesis using zebrafish embryos. We also examined their ability to inhibit breast cancer cells induced angiogenesis using a zebrafish xenograft breast tumor model.
Thesis Defense Jin Ma
September 30th, 2021
Jin Ma is defending her thesis on September 30th at 12:30
TGF-beta signaling in endothelial cells and angiogenesis
Promotor: Peter ten Dijke
Co-promotor: Gonzalo Sanchez Duffhues