Angiogenesis is regulated by the dynamic interaction between endothelial cells (ECs). Hippo-Yes-associated protein (YAP) signalling has emerged as a key pathway that controls organ size and tissue growth by mediating cell contact inhibition. However, the role of YAP in EC has not been defined yet. Here, we show expression of YAP in the developing front of mouse retinal vessels. YAP subcellular localization, phosphorylation and activity are regulated by VE-cadherin-mediated-EC contacts. This VE-cadherin-dependent YAP phosphorylation requires phosphoinositide 3-kinase-Akt activation. We further identify angiopoietin-2 (ANG-2) as a potential transcriptional target of YAP in regulating angiogenic activity of EC in vitro and in vivo. Overexpression of YAP-active form in EC enhances angiogenic sprouting, and this effect is blocked by ANG-2 depletion or soluble Tie-2 treatment. These findings implicate YAP as a critical regulator in angiogenesis and provide new insights into the mechanism coordinating junctional stability and angiogenic activation of ECs.
Bibliographical noteFunding Information:
This research was supported by Basic Science Reseatch Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2012R1A2A1A01002916; NRF-2013M3A9B6046563), by the Bio and Medical Technology Development Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technoligy (MEST) (NRF-2011-0019267), and by a grant (A085136) from the Korea Health 21 R&D Project, Ministry of Health and Welfare of the Republic of Korea. This work was also supported in part by the Brain Korea 21(BK21) PLUS program. Hyun-Jung Choi, Haiying Zhang, Kyu-Sung Choi, and Vijayendra Agrawal are fellowship awardee by BK21 PLUS program.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)