Role of Integrins alpha 1 beta 1 and alpha 2 beta 1 in Wound and Tumor Angiogenesis in Mice

摘要

Integrins are transmembrane receptors composed of one alpha subunit and one beta subunit and are involved in cellular growth, differentiation, and apoptosis. The collagen-binding integrins alpha 1 beta 1 and alpha 2 beta 1 have been shown to regulate wound and tumor vascularization by different mechanisms. In this study, we assessed wound and tumor vascularization in mice with genetic ablation of both integrin subunits alpha 1 and alpha 2, which resulted in Loss of integrins alpha 1 beta 1 and ant Wound angiogenesis was investigated in excisional wounds that were inflicted on the back skin of control and mice lacking integrin alpha 1 beta 1 and alpha 2 beta 1. Mutant mice displayed reduced wound angiogenesis, which correlated with decreased macrophage numbers at 3 and 7 days after injury, and showed significantly attenuated vascularization of sponge implants. Angiogenesis induced by tumors arising from intradermal injection of B16 F1 melanoma cells was also reduced in comparison to controls 7 days after injection. This reduction in angiogenesis correlated with increased Levels and activity of circulating matrix metalloproteinase 9 and elevated angiostatin levels in plasma of mutant mice, which reduced endothelial cell proliferation. Ex vivo mutant aortic ring explants developed significantly fewer and thinner aortic sprouts with fewer branch points than controls because of impaired endothelial cell proliferation. In conclusion, the loss of integrins alpha 1 beta 1 and alpha 2 beta 1 in mice results in reduced wound and tumor angiogenesis by cell-autonomous and extrinsic mechanisms.