| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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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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