Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neovascularization.

ABSTRACT:

Background

Sprouting angiogenesis is a key process driving blood vessel growth in ischemic tissues and an important drug target in a number of diseases, including wet macular degeneration and wound healing. Endothelial cells forming the sprout must develop front-rear polarity to allow sprout extension. The adaptor proteins Nck1 and 2 are known regulators of cytoskeletal dynamics and polarity, but their function in angiogenesis is poorly understood. Here, we show that the Nck adaptors are required for endothelial cell front-rear polarity and migration downstream of the angiogenic growth factors VEGF-A and Slit2.

Methods and results

Mice carrying inducible, endothelial-specific Nck1/2 deletions fail to develop front-rear polarized vessel sprouts and exhibit severe angiogenesis

SUBMITTER: Dubrac A 

PROVIDER: S-EPMC4729599 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature