2007 Homer W. Smith Award

Al‐Awqati, Qais

doi:10.1681/asn.2007111195

Cited by 14 publications

(11 citation statements)

References 28 publications

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“…The addition of anti-hensin antibodies prevents the acid-induced translocation of the Cl Ϫ /HCO 3 Ϫ exchanger from the apical to basolateral membrane, which is a conversion of ␤-to ␣-intercalated cells (1,47). Recently, the transformation of ␤-to ␣-intercalated cells was thought to be a terminal differentiation from "protoepithelium," a single-layered structure with polarized localization of membrane proteins and lipids, to a "more mature epithelium" that exhibits microvilli and exocytosis or endocytosis on apical membranes (2,47); hensin has been indicated as being involved in controlling this epithelial terminal differentiation (1,2). In zebrafish embryos, HR cells are responsible for excreting metabolic acids, similar to ␣-intercalated cells in mammalian kidneys.…”

Section: Discussionmentioning

confidence: 99%

“…In zebrafish embryos, HR cells are responsible for excreting metabolic acids, similar to ␣-intercalated cells in mammalian kidneys. The increased HR cell number during systemic acidosis is achieved by cell proliferation and cell differentiation; therefore, it would be interesting, in the future, to investigate if hensin, which is expressed in many tissues, including the kidneys, skin, gastrointestinal tract, lungs, and neurons (2,47), also mediates this process in zebrafish HR cells.…”

Section: Discussionmentioning

confidence: 99%

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Functional regulation of H⁺-ATPase-rich cells in zebrafish embryos acclimated to an acidic environment

Horng

Hwang

2009

American Journal of Physiology-Cell Physiology

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It is important to maintain internal pH homeostasis in biological systems. In our previous studies, H(+)-ATPase-rich (HR) cells were found to be responsible for proton secretion in the skin of zebrafish embryos during development. In this study, zebrafish embryos were exposed to acidic and basic waters to investigate the regulation of HR cell acid secretion during pH disturbances. Our results showed that the function of HR cells on the skin of zebrafish embryos can be upregulated in pH 4 water not only by increasing the cell number but also by enlarging the acid-secreting function of single cells. We also identified an "alveolar-type" apical opening under scanning electron microscopy observations of the apical membrane of HR cells, and the density and size of the alveolar type of apical openings were also increased in pH 4 water. p63 and PCNA immunostaining results also showed that additional HR cells in pH 4 water may be differentiated not only from ionocyte precursor cells but also newly proliferating epithelial stem cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Functional regulation of H⁺-ATPase-rich cells in zebrafish embryos acclimated to an acidic environment

Horng

Hwang

2009

American Journal of Physiology-Cell Physiology

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“…A baseline protective function of DMBT1 is suggested by studies showing that it prevents bacterial invasion in vitro, intestinal inflammation in vivo, and that DMBT1 polymorphisms giving rise to a shortened protein variant may predispose to Crohn's disease (85)(86)(87)(88). Moreover, DMBT1 interacts with several components of the innate immunity, which include SP-D, SP-A, IgA, lactoferrin, mucin 5B (MUC5B), and C1q (56,60,81,(89)(90)(91)(92)(93)(94)(95)(96)(97), and the lectin galectin-3 and TFF2 as accessory proteins in the mediation of differentiation and regeneration (76,(98)(99)(100)(101). Additionally, DMBT1 stimulates recruitment of alveolar macrophages and interacts also with the bacterial proteins antigen I/II, SspA and SspB (102)(103)(104)(105).…”

Section: The Pattern Recognition Molecule Dmbt1mentioning

confidence: 99%

Natural pattern recognition mechanisms at epithelial barriers and potential use in nanomedicine

Casella¹,

Tuttolomondo²,

Høilund‐Carlsen³

et al. 2014

European Journal of Nanomedicine

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“…The mechanisms by which IC respond to variations in acid/base status by changing the polarized expression of the V‐ATPase remain poorly understood, but the Al‐Awqati laboratory has shown that this process is mediated by a protein called hensin. This protein is secreted into the extracellular environment where it polymerizes and binds to cell surface integrins that in turn induce terminal differentiation signals resulting in transformation of B‐IC into A‐IC (53).…”

Section: Vacuolar H+‐adenosine Triphosphatase Trafficking In Intercalmentioning

confidence: 99%

Sensing, Signaling and Sorting Events in Kidney Epithelial Cell Physiology

Brown

Breton

Ausiello

et al. 2009

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The kidney regulates body fluid, ion and acid/base homeostasis through the interaction of a host of channels, transporters and pumps within specific tubule segments, specific cell types and specific plasma membrane domains. Furthermore, renal epithelial cells have adapted to function in an often unique and challenging environment that includes high medullary osmolality, acidic pHs, variable blood flow and constantly changing apical and basolateral 'bathing' solutions. In this review, we focus on selected protein trafficking events by which kidney epithelial cells regulate body fluid, ion and acid-base homeostasis in response to changes in physiological conditions. We discuss aquaporin 2 and G-protein-coupled receptors in fluid and ion balance, the vacuolar H 1 -adenosine triphosphatase (V-ATPase) and intercalated cells in acid/base regulation and acidification events in the proximal tubule degradation pathway. Finally, in view of its direct role in vesicle trafficking that we outline in this study, we propose that the V-ATPase itself should, under some circumstances, be considered a fourth category of vesicle 'coat' protein (COP), alongside clathrin, caveolin and COPs. Trafficking of Aquaporin 2 -the Vasopressin-Responsive Water ChannelAquaporin 2 is the vasopressin (VP)-sensitive water channel that is involved in urinary concentration. After VP is released from the posterior pituitary upon an increase in plasma osmolality or decrease in volume, it interacts with the vasopressin type 2 receptor (V2R) on collecting duct principal cells, increases cyclic AMP (cAMP), induces protein kinase A (PKA) phosphorylation of AQP2 at serine 256 in the C-terminus and shifts AQP2 localization from intracellular vesicles to the plasma membrane (Figure 1) (1-3). This greatly increases epithelial water permeability and allows urinary concentration to occur by osmotic equilibration of the luminal fluid with the hypertonic interstitium. Defects in the V2R/AQP2 signaling pathway lead to nephrogenic diabetes insipidus -a disease in which over 15 L of dilute urine can be produced each day (4,5).

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2007 Homer W. Smith Award

Cited by 14 publications

References 28 publications

Functional regulation of H⁺-ATPase-rich cells in zebrafish embryos acclimated to an acidic environment

Functional regulation of H⁺-ATPase-rich cells in zebrafish embryos acclimated to an acidic environment

Natural pattern recognition mechanisms at epithelial barriers and potential use in nanomedicine

Sensing, Signaling and Sorting Events in Kidney Epithelial Cell Physiology

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2007 Homer W. Smith Award

Cited by 14 publications

References 28 publications

Functional regulation of H+-ATPase-rich cells in zebrafish embryos acclimated to an acidic environment

Functional regulation of H+-ATPase-rich cells in zebrafish embryos acclimated to an acidic environment

Natural pattern recognition mechanisms at epithelial barriers and potential use in nanomedicine

Sensing, Signaling and Sorting Events in Kidney Epithelial Cell Physiology

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Product

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Functional regulation of H⁺-ATPase-rich cells in zebrafish embryos acclimated to an acidic environment

Functional regulation of H⁺-ATPase-rich cells in zebrafish embryos acclimated to an acidic environment