2004 Fiscal Year Final Research Report Summary
Gene analysis and molecular drug discovery of ADPKD
| Project/Area Number |
15591713
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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 | Teikyo University |
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Principal Investigator |
HORIE Shigeo Teikyo Univ, Dept. of Urology. School of Medicine, Professor and Chairman, 医学部, 教授 (40190243)
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| Project Period (FY) |
2003 – 2004
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| Keywords | ADPKD / polycystin-1 / endothelin-1 / MAPK / PWV / vascular endothelial function |
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| Research Abstract |
In the Pkd1^<-/-> kidney, the renal parenchyma of Pkd1^<-/-> had numerous cysts. The hearts of Pkd1^<-/-> had a double-outlet right ventricle (DORV) and ventricular septal defect (VSD). It is well known that DORV is observed in endothelin-l(ET-1) deficient mice. ET-1 regulate ERK activation. So, to investigate whether polycystin-1 would regulate the ET-1 pathway, mouse embryonic fibroblast (MEF) was stimulated with ET-1 and the phosphorylation of ERK was examined with gel shift assay. The phosphorylation was hardly admitted in Pkd1^<-/-> MEF compared with Pkd1^<+/+> and Pkd1^<+/-> MEF. Moreover, the high osmotic pressure stimulation is known to the stimulation that activates ERK excluding ET-1. When the activation of ERK in the high osmotic pressure stimulation was examined to examine whether it was the one ET-1 peculiar a previous result, the phosphorylation was hardly admitted in Pkd1^<-/-> MEF compared with Pkd1^<+/+> and Pkd1^<+/-> MEF. MAPK activates AP-1, and adjusts the gene expression such as c-MYC. Pkd1^<-/-> has been intentionally decreasing the appearance of c-MYC by heart compared with a wild type. These results suggested that polycystin-1 take part in Pkd1^<-/-> in the signal transmission of MAPK/ERK2.
Ankle Brachial Index (ABI) and Pulse Wave Velocity (PWV) were measured for 18 ADPKD patients. These data showed good reverse-correlation between PWV, ABI and Ccr (PWV : P=0.0006, ABI : P=0.0285). Moreover, renal volume intentionally correlated only to PWV (P=0.0364).
These data suggests that the relation to the progress of renal failure and vascular endothelial function, and the possibility of a molecular drug development was expected.
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Research Products
(8 results)
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[Journal Article] Evidence for the presence of angiogenin in human testis2004
Author(s)
Koga K, Osuga Y, Yano T, Ikezuki Y, Yoshino O, Hirota Y, Hirata T, Horie S, Ayabe T, Tsutsumi O, Taketani Y
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Journal Title
J Androl. 25(3)
Pages: 369-374
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Evidence for the presence of angiogenin in human testis.2004
Author(s)
Koga K, Osuga Y, Yano T, Ikezuki Y, Yoshino O, Hirota Y, Hirata T, Horie S, Ayabe T, Tsutsumi O, Taketani Y.
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Journal Title
J Androl. 25(3)
Pages: 369-74
Description
「研究成果報告書概要(欧文)」より
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