Aquaporin 1 is required for hypoxia-inducible angiogenesis in human retinal vascular endothelial cells

Kikuchi, Kentaro; Yagui, Kazuo; Tanaka, Asami; Yoshihara, Kei; K, Ishikawa; Takahashi, Kazuo; Bujo, Hideaki; Sakurai, Kenichi; Saitō, Yasushi

doi:10.1016/j.mvr.2007.12.003

Cited by 67 publications

(44 citation statements)

References 32 publications

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“…On the other hand, deletion of a single AQP might not significantly affect cell water transport because other known or still unidentified AQPs could undergo compensatory upregulation. The advantages of siRNA technology for specific and effective inhibition of endogenous genes expression are becoming apparent (24), and it has been used for assessing the role of aquaporins in water transport in cholangiocytes (6,30), colonocytes (19), astrocytes (26), and vascular endothelial cells (17). Using this technology, we provide direct experimental evidence supporting the notion that AQP8 mediates the water transport necessary for canalicular bile secretion, i.e., AQP8 knockdown caused a decrease in basal canalicular volume (Fig.…”

Section: Discussionsupporting

confidence: 63%

Knockdown of hepatocyte aquaporin-8 by RNA interference induces defective bile canalicular water transport

Larocca¹,

Soria²,

Espelt³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Larocca MC, Soria LR, Espelt MV, Lehmann GL, Marinelli RA. Knockdown of hepatocyte aquaporin-8 by RNA interference induces defective bile canalicular water transport. Am J Physiol Gastrointest Liver Physiol 296: G93-G100, 2009. First published October 23, 2008 doi:10.1152/ajpgi.90410.2008 water channels, which are expressed in rat hepatocyte bile canalicular membranes, are involved in water transport during bile formation. Nevertheless, there is no conclusive evidence that AQP8 mediates water secretion into the bile canaliculus. In this study, we directly evaluated whether AQP8 gene silencing by RNA interference inhibits canalicular water secretion in the human hepatocyte-derived cell line, HepG2. By RT-PCR and immunoblotting we found that HepG2 cells express AQP8 and by confocal immunofluorescence microscopy that it is localized intracellularly and on the canalicular membrane, as described in rat hepatocytes. We also verified the expression of AQP8 in normal human liver. Forty-eight hours after transfection of HepG2 cells with RNA duplexes targeting two different regions of human AQP8 molecule, the levels of AQP8 protein specifically decreased by 60 -70%. We found that AQP8 knockdown cells showed a significant decline in the canalicular volume of ϳ70% (P Ͻ 0.01), suggesting an impairment in the basal (nonstimulated) canalicular water movement. We also found that the decreased AQP8 expression inhibited the canalicular water transport in response either to an inward osmotic gradient (Ϫ65%, P Ͻ 0.05) or to the bile secretory agonist dibutyryl cAMP (Ϫ80%, P Ͻ 0.05). Our data suggest that AQP8 plays a major role in water transport across canalicular membrane of HepG2 cells and support the notion that defective expression of AQP8 causes bile secretory dysfunction in human hepatocytes.HepG2; human liver; bile secretion; dibutyryl cAMP BILE IS COMPOSED OF 98% WATER, which is mainly secreted by hepatocytes at bile canaliculi. Water transport at this level is driven by transient osmotic gradients generated across the hepatocyte membrane by active solute transport (1). Aquaporins (AQPs) are a family of integral membrane proteins that facilitate the osmotically induced water transport through cell membranes (18). At least 13 mammalian aquaporins have been identified in diverse human and animal cells. Rat hepatocytes express four AQPs, i.e., AQP8 (9, 13, 16), AQP9 (10, 16), AQP11 (14), and AQP0 (16). AQP8 is localized, as a glycosylated 34-kDa protein, in intracellular vesicles and at the canalicular plasma membrane (9, 13, 16). There is experimental evidence suggesting that AQP8 facilitates the canalicular water transport during hepatocyte bile formation (16) and that the defective expression of hepatocyte AQP8 may contribute to bile secretory dysfunction in cholestasis (4,5,20). Nevertheless, conclusive evidence for AQP8 involvement in bile canalicular water transport should come from studies performed in hepatocytes lacking AQP8 expression. Recently, it has been described that hepatocytes from AQP8-null mice show simila...

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Section: Discussionsupporting

confidence: 63%

Knockdown of hepatocyte aquaporin-8 by RNA interference induces defective bile canalicular water transport

Larocca¹,

Soria²,

Espelt³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Endothelial cells in the olfactory region of the nasal cavity of the rat have been shown to be leaky and to express massive amounts of AQP1 , indirectly suggesting a negative correlation between barrier property and AQP1 expression. Kaneko et al (2007) have reported that, under hypoxia, the levels of AQP1 mRNA and protein expression significantly increase in cultured retinal microvessel endothelial cells. This once again supports the view that AQP1 expression in endothelial cells is associated with compromised barrier properties.…”

Section: Aquaporins In Astrocytes and Endothelial Cellsmentioning

confidence: 99%

“…This once again supports the view that AQP1 expression in endothelial cells is associated with compromised barrier properties. In addition, a reduction of AQP1 expression inhibits tube formation suggesting an involvement of AQP1 in hypoxiainducible angiogenesis (Kaneko et al 2007).…”

Section: Aquaporins In Astrocytes and Endothelial Cellsmentioning

confidence: 99%

Brain endothelial cells and the glio-vascular complex

et al. 2008

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We present and discuss the role of endothelial and astroglial cells in managing the blood-brain barrier (BBB) and aspects of pathological alterations in the BBB. The impact of astrocytes, pericytes, and perivascular cells on the induction and maintenance of the gliovascular unit is largely unidentified so far. An understanding of the signaling pathways that lie between these cell types and the endothelium and that possibly are mediated by components of the basal lamina is just beginning to emerge. The metabolism for the maintenance of the endothelial barrier is intimately linked to and dependent on the microenvironment of the brain parenchyma. We report the structure and function of the endothelial cells of brain capillaries by describing structures involved in the regulation of permeability, including transporter systems, caveolae, and tight junctions. There is increasing evidence that caveolae are not only vehicles for endo- and transcytosis, but also important regulators of tight-junction-based permeability. Tight junctions separate the luminal from the abluminal membrane domains of the endothelial cell ("fence function") and control the paracellular pathway ("gate function") thus representing the most significant structure of the BBB. In addition, the extracellular matrix between astrocytes/pericytes and endothelial cells contains numerous molecules with inherent signaling properties that have to be considered if we are to improve our knowledge of the complex and closely regulated BBB.

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“…Probably, non-damaged endothelial cells with stronger AQP1 reaction migrate into the damaged tissue after phagocytosis of degenerated endothelial cells by ACPase reactive macrophages which temporally migrated in and around the damaged area. Indeed, it has been reported that AQP1 promotes microvascular generation by accelerating cell migration in tumor models (29), and that a lack of AQP1 inhibits angiogenesis in vivo and in vitro (4,14). However, the revasculature process incident to tissue remodeling has not yet been elucidated.…”

Section: Discussionmentioning

confidence: 99%

Immunoexpression of aquaporin-1 in the rat periodontal ligament during experimental tooth movement

et al. 2012

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Aquaporin 1 is required for hypoxia-inducible angiogenesis in human retinal vascular endothelial cells

Cited by 67 publications

References 32 publications

Knockdown of hepatocyte aquaporin-8 by RNA interference induces defective bile canalicular water transport

Knockdown of hepatocyte aquaporin-8 by RNA interference induces defective bile canalicular water transport

Brain endothelial cells and the glio-vascular complex

Immunoexpression of aquaporin-1 in the rat periodontal ligament during experimental tooth movement

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