Role of claudins in electrolyte transports through paracellular pathways of the renal tubule
| Project/Area Number |
17590840
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Jichi Medical University |
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Principal Investigator |
MUTO Shigeaki Jichi Medical University, School of Medicine, Nephrology, Associate Professor, 医学部, 助教授 (40190855)
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| Co-Investigator(Kenkyū-buntansha) |
MIYATA Yukio Jichi Medical University, School of Medicine, Nephrology, Visiting Researcher, 医学部, 客員研究員 (00285777)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | tight junction / claudin-2 / proximal tubule / Na / Cl transport |
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| Research Abstract |
Claudin-2 is highly expressed in tight junctions of mouse proximal tubule composing of a leaky epithelium with unique paracellular permeability properties that underlies its high rate of NaCl reabsorption. To investigate the functional role of claudin-2 in the paracellular NaCl transport in this nephron segment, we generated mice lacking claudin-2 [Cld2^<-/->] by gene targeting disruption and compared their morphological and functional properties with their wild-type littermates [Cld2^<+/+>]. The Cld2^<-/-> mice had grossly normal appearance, activity, growth, and behavior. Light microscopic findings exhibited no gross histological abnormalities in the Cld2^<-/-> kidney. Ultrathin section and freeze-fracture replica electron microscopy revealed that, similar to Cld2^<+/+> mice, the proximal tubule of Cld2^<-/-> mice was characterized by poorly-developed tight junctions with one or two continuous strands. In sharp contrast, the functional studies in isolated perfused S2 segments of proximal tubules showed that net transepithelial absorptions of Na^+, Cl^-, and water were significantly decreased in Cld2^<-/-> mice and that the claudin-2-deficiency led to an increase in paracellular shunt resistance without affecting apical or basolateral membrane resistances. Moreover, the Na^+-selectivity of paracellular permeability of proximal tubules in Cld2^<+/+> mice was converted to be Cl^--selective in Cld2^<-/-> mice. Cld2^<-/-> mice intravenously given 2% NaCl exhibited exaggerated urinary NaCl loss compared with Cld2^<+/+> mice, although Cld2^<-/-> mice under free access to water and food showed urinary excretions of NaCl with a similar magnitude to Cld2^<+/+> mice. We conclude that claudin-2 constitutes leaky and Na^+-selective paracellular channels within tight junctions of mouse proximal tubule.
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Report
(3 results)
Research Products
(12 results)
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[Journal Article] Peritoneal injury by methylglyoxal in peritoneal dialysis2006
Author(s)
Hirahara, I., Kusano, E., Yanagiba, S., Miyata, Y., Ando, Y., Muto, S., Asano, Y.
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Journal Title
Peritoneal Dialysis International 26
Pages: 380-392
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Effect of oral glucose administration on serum potassium concentration in hemodialysis patients2005
Author(s)
Muto, S., Sebata, K., Watanabe, H., Shoji, F, Yamamoto, Y., Ohashi, M., Yamada, T., Matsumoto, H., Mukouyama, T., Yonekura, T., Namiki, S., Kusano, E.
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Journal Title
American Journal of Kidney Diseases 46
Pages: 697-705
Description
「研究成果報告書概要(欧文)」より
Related Report
