| Project/Area Number |
15K19357
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Department of Clinical Research, National Hospital Organization Nagasaki Medical Center |
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Principal Investigator |
AIBA YOSHIHIRO 独立行政法人国立病院機構(長崎医療センター臨床研究センター), 臨床研究センター, 研究員 (70450955)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 原発性胆汁性胆管炎 / 原発性胆汁性肝硬変 / GWAS / CTSZ / カテプシン / 重症化機構 / 疾患関連遺伝子 / 肝不全 |
|---|
| Outline of Final Research Achievements |
We identified NELFCD/CTSZ as loci associated with progression to jaundice and liver failure (end-stage) in primary biliary cholangitis (PBC).Serum CTSZ levels were significantly higher in end-stage than other stages (early-stage or late-stage) in PBC. The levels of CTSZ were significantly correlated with those of aspartate transaminase, total bilirubin, platelet count, and albumin in the blood of PBC. The levels of CTSZ protein in hepatocytes were increased with the progression of PBC. In end-stage PBC, the localization of CTSZ was translocated from peri-bile canalicular region to inner cytoplasmic region of hepatocytes, where a part of CTSZ was not co-localized with endsomal/lysosomal vesicles. Chloroquine and amino acid starvation enhanced cell death in CTSZ transfected HuH7. These results indicated that the increased expression and altered localization of CTSZ might be implicated in the progression of PBC via cell death.
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