Contribution of Endothelial Laminin-Binding Integrins to Cellular Processes Associated with Angiogenesis

Endothelial cells engage extracellular matrix and basement membrane components through integrin-mediated adhesion to promote angiogenesis. Angiogenesis involves the sprouting of endothelial cells from pre-existing vessels, their migration into surrounding tissue, the upregulation of angiogenesis-associated genes, and the formation of new endothelial tubes. To determine whether the endothelial laminin-binding integrins, alpha 6 beta 4, and alpha 3 beta 1 contribute to these processes, we employed RNAi technology in organotypic angiogenesis assays, as well in migration assays, in vitro. The endothelial depletion of either alpha 6 beta 4 or alpha 3 beta 1 inhibited endothelial sprouting, indicating that these integrins have non-redundant roles in this process. Interestingly, these phenotypes were accompanied by overlapping and distinct changes in the expression of angiogenesis-associated genes. Lastly, depletion of alpha 6 beta 4, but not alpha 3 beta 1, inhibited migration. Taken together, these results suggest that laminin-binding integrins regulate processes associated with angiogenesis by distinct and overlapping mechanisms.

Automated summary

Endothelial cells engage with extracellular matrix and basement membrane components through integrins, promoting angiogenesis. Laminin-binding integrins α6β4 and α3β1 have non-redundant roles in this process, affecting cell sprouting, migration, and gene expression differently.