Pro-angiogenic Activities of CYR61 (CCN1) Mediated through Integrins αvβ3and α6β1in Human Umbilical Vein Endothelial Cells

摘要: CYR61 (CCN1) is an extracellular matrix-associated protein of the CCN family, which also includes CTGF (CCN2), NOV (CCN3), WISP-1 (CCN4), WISP-2 (CCN5), and WISP-3 (CCN6). Purified induces neovascularization in corneal implants, Cyr61-null mice suffer embryonic death due to vascular defects, thus establishing that important regulator angiogenesis. Aberrant expression ofCyr61 associated with breast cancer, wound healing, diseases such as atherosclerosis restenosis. In culture, functions through integrin-mediated pathways promote cell adhesion, migration, proliferation. Here we show can survival tubule formation human umbilical vein endothelial cells. Furthermore, have dissected integrin receptor requirements respect its pro-angiogenic activities. Thus, CYR61-induced adhesion occur interaction α6β1 early passage cells integrins not been activated. By contrast, are activated by phorbol ester or growth factor, CYR61-promoted survival, factor-induced mitogenesis, all mediated αvβ3. These findings indicate activation-dependent ligand αvβ3 activation-independent these differentially mediate activities CYR61. help define mechanisms acts angiogenic regulator, provide a molecular interpretation for loss integrity increased apoptosis inCyr61-null mice, underscore importance development homeostasis system.