| Project/Area Number |
16390206
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
NARUSE Satoru Nagoya University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (50180550)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KONDO Takaharu Research Center of Health, Physical Fitness, and Sports, Professor, 総合保健体育科学センター, 教授 (20135388)
ISHIGURO Hiroshi Research Center of Health, Physical Fitness, and Sports, Associate Professor, 総合保健体育科学センター, 助教授 (90303651)
NAGAO Shizuko Fujita Health University, Education and Research Center of Animal Models for Human Diseases, Assistant Professor, 疾患モデル教育研究センター, 講師 (20183527)
FURUYA Sonoko National Insitute for Physiological Sciences, Research Associate, 生理学研究所, 助手 (20096952)
NAGAHAMA Masato Suzuka University of Medical Science, Medical Engineering, Professor, 医用工学部, 教授 (50198355)
|
|---|
| Project Period (FY) |
2004 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2006: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2005: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥8,600,000 (Direct Cost: ¥8,600,000)
|
|---|
| Keywords | chronic pancreatitis / water tranport / HCO_3- transport / CFTR / Na^+-H^+ exchange (NHE) / SLC26 transporters / cystic fibrosis / fibrocystin / 遺伝子変異 / RNAi / SLC26 / 遺伝子多型 / センサー分子 |
|---|
| Research Abstract |
In order to elucidate molecular pathogenesis of chronic pancreatitis, we investigated functional effects of mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) and other ion transporters and fibrocystin.
1. The entire coding regions of the CFTR gene were analyzed in 65 patients with chronic pancreatitis. Pancreatitis-associated mutations or polymorphisms were identified.
2. A finger sweat chloride test, using a highly sensitive chloride electrode, was developed for detecting a high-risk group of chronic pancreatitis.
3. A reciprocal regulatory interaction between CFTR and SLC26 transporters (SLC26A3 and SLC26A6) was demonstrated in HEK293 cells.
4. Mouse slc26a3 mediated a coupled 2C1^-11HCO_3exchanger, while slc26a6 acted as a 1C^-/2HCO_3exchanger.
5. The entire sequence of the guinea pig CFTR gene was determined. Specific RNA interference of the CFTR reduced pancreatic ductal fluid secretion by 50%.
6. Short-chain n-alcohol augmented or reduced pancreatic ductal fluid secretion by activating or inhibiting plasma membrane Ca^<2+> channel.
7. The Na^+-H^+ exchange played an important role in acidifying pancreatic juice in A ΔF508 CF mice.
8. The developmental morphology of the pancreas in polycystic kidney (PKC) rats with a mutation of the fibrocystin gene was examined. Abnormal Ca^<2+> signal and fluid responses were observed in pancreatic ducts isolated from PKC rats.
|
