2002 Fiscal Year Final Research Report Summary
CRYSTAL CELL INTERACTION BETWEEN RENAL EPITHELIAL CELLS AND CALCIUM OXALATE CRYSTALS USING THE ANIMAL MODEL FOR CALCIUM OXALATE STONE
| Project/Area Number |
13671630
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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 |
Urology
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
YAMAGUCHI Satoshi Asahikawa Medical College, Dept. of Urology, Assistant Professor, 医学部, 講師 (40230354)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Urolithiasis / Crystal cell interaction / Experimental model / Calcium oxalate stone / Flowcytometry / phosphatidylserine / caspase / Chondroitin polysulfate |
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| Research Abstract |
In 2001, a study was conducted to establish a model of renal stones induced by calcium oxalate that would be suitable for investigating crystal-cell interactions between calcium oxalate crystals and renal epithelium. In that study, it was possible to determine conditions under which calcium oxalate crystaluria can be induced while minimizing renal injury, by adjusting the conditions used in conventional in vivo experiments. More specifically, it seemed to be suitable to administer 0.1-0.2 % ethylene glycol plus 1.0 % ammonium chloride for 9 days or 0.4 % ethylene glycol alone for 14 days. In addition to the studies of crystal-cell interactions conducted in vitro, determination of these conditions made it possible to endorse in vivo experiment.
In 2002, the following two experiments were carried out.
Experiment 1: A study on the cell membrane of the renal collecting duct cells exposed to calcium oxalate crystals. Under conditions inducing the formation of calcium oxalate crystals, changes
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in the distribution of phosphatidylserine on the cell membrane of the renal collecting duct cells were examined by flowcytometry and fluorescent microscope. It was confirmed that phosphatidylserine expressing cells gradually increased with urinary excretion of oxalate and calcium oxalate crystals. Caspase family, one of the intracellular signal transduction systems for apoptosis, was also activated.
Experiment 2: Effects on chondroitin polysulfate to prevent the adhesion of calcium oxalate crystals to the renal epithelial cells. When rats were treated with chondroitin polysulfate under the same conditions as Experiment 1, phosphatidylserine exposure on the renal collecting duct cells and the activities of caspase 3, 8, and 9 tended to be suppressed comparing to the untreated control groups. These results indicate that the effects of mild cell injury on crystal-cell interactions can be quantitatively analyzed by in vivo experiment. It seems likely that the small injury of the renal collecting duct cells caused by calcium oxalate crystals can be controlled by chondroitin polysulfate, leading to suppression of stone formation. Less
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