Aquaporin-1 facilitates angiogenic invasion in the pathological neovasculature that accompanies cirrhosis.

Publication Type:

Journal Article


Hepatology (Baltimore, Md.), Volume 52, Issue 1, p.238-48 (2010)


Animalsdigestive disease, digestive deseases Aquaporin 1digestive disease, digestive deseases Cell Membranedigestive disease, digestive deseases Cell Membrane Permeabilitydigestive disease, digestive deseases Cell Movementdigestive disease, digestive deseases Cells, Cultureddigestive disease, digestive deseases Endothelium, Vasculardigestive disease, digestive deseases Fibroblast Growth Factorsdigestive disease, digestive deseases Humansdigestive disease, digestive deseases Liverdigestive disease, digestive deseases Liver Cirrhosisdigestive disease, digestive deseases Micedigestive disease, digestive deseases Mice, Inbred C57BLdigestive disease, digestive deseases Neovascularization, Pathologicdigestive disease, digestive deseases Osmosisdigestive disease, digestive deseases RNA, Small Interferingdigestive disease, digestive deseases Water


Increasing evidence suggests that hepatic fibrosis and pathological angiogenesis are interdependent processes that occur in parallel. Endothelial cell invasion is requisite for angiogenesis, and thus studies of the mechanisms governing liver endothelial cell (LEC) invasion during cirrhosis are of great importance. Emerging research implicates amoeboid-type motility and membrane blebbing as features that may facilitate invasion through matrix-rich microenvironments. Aquaporins (AQPs) are integral membrane water channels, recognized for their importance in epithelial secretion and absorption. However, recent studies also suggest links between water transport and cell motility or invasion. Therefore, the purpose of this study was to test the hypothesis that AQP-1 is involved in amoeboid motility and angiogenic invasion during cirrhosis. AQP-1 expression and localization was examined in normal and cirrhotic liver tissues derived from human and mouse. AQP-1 levels were modulated in LEC using retroviral overexpression or small interfering RNA (siRNA) knockdown and functional effects on invasion, membrane blebbing dynamics, and osmotic water permeability were assayed. Results demonstrate that AQP-1 is up-regulated in the small, angiogenic, neovasculature within the fibrotic septa of cirrhotic liver. AQP-1 overexpression promotes fibroblast growth factor (FGF)-induced dynamic membrane blebbing in LEC, which is sufficient to augment invasion through extracellular matrix. Additionally, AQP-1 localizes to plasma membrane blebs, where it increases osmotic water permeability and locally facilitates the rapid, trans-membrane flux of water. CONCLUSION: AQP-1 enhances osmotic water permeability and FGF-induced dynamic membrane blebbing in LEC and thereby drives invasion and pathological angiogenesis during cirrhosis.