Role of AQP1 in endotoxemia-induced acute kidney injury

Wang, Weidong; Li, Chunling; Summer, Sandra N.; Falk, Sandor; Wang, Wei; Ljubanović, Danica Galešić; Schrier, Robert W.

doi:10.1152/ajprenal.00036.2008

Cited by 62 publications

(52 citation statements)

References 17 publications

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“…GFR reduction by inflammatory stimuli has been reported previously (19)(20)(21). In clinical trials, GFR reduction was reported during inflammation especially when blood flow and/or blood pressure were substantially reduced, for example, in hypodynamic septic shock associated with a lowered cardiac output, which leads to a significant reduction in the clearance of a variety of drugs (34).…”

Section: Discussionmentioning

confidence: 76%

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Impact of Lipopolysaccharide-Induced Inflammation on the Disposition of the Aminocephalosporin Cefadroxil

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Smith

2013

Antimicrob Agents Chemother

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bThe purpose of this study was to determine if the disposition of cefadroxil, an ␣-amino-containing ␤-lactam antibiotic, changes during lipopolysaccharide (LPS)-induced acute inflammation. Six hours after LPS or saline treatment, mice received 1 nmol/g cefadroxil intravenously along with inulin for glomerular filtration rate (GFR) determination. Serial blood samples, along with tissue and urine samples, were collected at predetermined time points. In order to determine inflammation-induced changes in GFR, renal tubular secretion, and reabsorption, it was necessary to coadminister 70 mg/kg probenecid. Changes in the expression of the mRNA of transporters involved in cefadroxil disposition in the kidneys and choroid plexus were also investigated 6 h after LPS treatment. The results demonstrated marked increases in blood, cerebrospinal fluid, and tissue cefadroxil concentrations with LPS treatment. Tissue-to-blood concentration ratios were decreased by 4.6-fold in the choroid plexus and by 2.5-fold in the kidneys during LPS-induced inflammation. Renal, but not choroid plexus, mRNA expression of peptide transporter 2, organic-anion transporter 1 (OAT1), OAT3, and multidrug resistance-associated protein 4 was mildly reduced in LPS-treated mice. The renal clearance of cefadroxil was substantially decreased by LPS treatment (3-fold). GFR was also reduced by 3-fold in LPS-treated mice, but no significant differences in the fractional reabsorption of cefadroxil and renal secretion once normalized by GFR were observed. These findings demonstrated that LPS-induced inflammation has a dramatic effect on the renal excretion of cefadroxil. It appears that changes in transporter expression played a minor role during LPS treatment but that renal dysfunction, associated with GFR reduction, was responsible for the substantial increase in plasma cefadroxil concentration-time profiles.

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Section: Discussionmentioning

confidence: 76%

“…Administration of LPS is known to induce significant reductions in the GFR and tubular function, as commonly observed in patients with septic shock (18)(19)(20)(21). It has also been reported that LPS treatment downregulates OAT transcripts and protein expression in the kidneys and upregulates PEPT2 transcripts in the choroid plexus (7,22).…”

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confidence: 91%

Impact of Lipopolysaccharide-Induced Inflammation on the Disposition of the Aminocephalosporin Cefadroxil

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Smith

2013

Antimicrob Agents Chemother

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“…AQP1 expression in the kidney could have a protective role in LPS induced endotoxemia (presence of LPS in the blood stream). Knock-out mice lacking AQP1 show a predisposition to endotoxemia-induced acute kidney injury [134]. Taken together, these data are adding pieces to the puzzle of emerging data for a role of AQPs and especially AQP9 in the immune response to bacterial infections.…”

Section: Lipopolysaccharide and Aquaporinsmentioning

confidence: 80%

Aquaporins in Infection and Inflammation

Holm¹

2016

Linköping University Medical Dissertations

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About the cover:The front cover displays a human, blood-derived macrophage stained for aquaporin 9.During the course of the research underlying this thesis, Angelika Holm was enrolled in Forum Scientium, a multidisciplinary doctoral programme at Linköping University Printed by LiU-Tryck, Linköping, Sweden, 2016 "Be brave, even if you're not, pretend to be. No one can tell the difference."To that young, awkward, tall girl who dared to dream of something else, something more:You did it. SUPERVISOR Elena VikströmDepartment of Clinical and Experimental Medicine Linköping University Linköping Sweden When cells of the innate immune system encounter pathogens they need to respond and prepare for migration and phagocytosis and do so through volume regulatory processes. The Gramnegative bacterium Pseudomonas aeruginosa utilizes a small molecule-based communication system, called quorum sensing (QS) to control the production of its virulence factors and biofilms. We found that P. aeruginosa with a complete QS system elicits a stronger phagocytic response in human blood-derived macrophages compared to its lasI-/rhlI-mutant lacking the production of the QS molecules N-butyryl-L-homoserine lactone (C4-HSL) and N-3-oxododecanoyl-L-homoserine lactone (3O-C12-HSL). Infection with P. aeruginosa further increases the expression of AQP9 and induces re-localisation of AQP9 to the front and trailing ends of macrophages. Moreover, the 3O-C12-HSL alone elevates the expression of AQP9, redistribute the water channel to the front and rear ends and increases the cell area and volume of macrophages. Both infection with the wild type P. aeruginosa and the treatment with 3O-C12-HSL change the nano-structural architecture of the AQP9 distribution in macrophages. ASSISTANT SUPERVISORS Karl-Eric MagnussonViruses use the intracellular machinery of the invaded cells to produce and assemble new viral bodies. Intracellular AQPs are localised in a membranes of cellular organelles to regulate their function and morphology. C3H10T1/2 fibroblasts transiently expressing green fluorescent protein (GFP)-AQP6 show a reduced expression of AQP6 after Hazara virus infection and an increased cell area. Overexpressing AQP6 in C3H10T1/2 cells reduces the infectivity of Hazara virus indicating that AQP6 expression has a protective role in virus infections.Ion and water channels in the epithelial cell lining tightly regulate the water homeostasis. In microscopic colitis (MC), patients suffer from severe watery diarrhoeas. For the first time, we have shown that the expression of AQP1, 8 and 11 and the sodium/hydrogen exchanger NHE1 are reduced in colonic biopsies from MC patients compared to healthy control individuals. Following treatment with the glucocorticoid budesonide the patients experienced a rapid recovery and we observed a restored or increased expression of the AQPs and NHE1 during treatment, suggesting a role for AQPs in the diarrhoeal mechanisms in MC.Taken together, this thesis provides new evidence on the importance of water homeostasis regulatio...

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“…For assessment of injury, 5-mm kidney sections were stained with periodic acid-Schiff. Acute tubular necrosis was determined in the outer stripe of the outer medulla and cortex using a semiquantitative scale in which the percentage of tubules showing epithelial necrosis, brush-border loss, and cast formation was assigned a score: 0 = normal, 1 = ,10%, 2 = 11-25%, 3 = 26-45%, 4 = 46-75%, and 5 = .76% (26,27).…”

Section: Histologymentioning

confidence: 99%