Analysis of molecular mechanisms involved in progression to jaundice and liver failure in primary biliary cholangitis

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19357
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Department of Clinical Research, National Hospital Organization Nagasaki Medical Center
• 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)
• Project Period (FY): 2015-04-01 – 2017-03-31
• 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

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.

Free Research Field

肝臓学