Analysis of fibrinogen function and storage kinetics using model cells of fibrinogen storage disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15945
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Shinshu University
• Principal Investigator: Arai Shinpei 信州大学, 学術研究院保健学系, 助教 (70866053)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: フィブリノゲン / 先天性フィブリノゲン低下症 / フィブリノゲン蓄積病 / フィブリン重合反応 / 小胞体ストレス応答

Outline of Final Research Achievements

Fibrinogen storage disease(FSD), in which fibrinogen accumulates in the endoplasmic reticulum of hepatocytes and causes hepatocellular damage and cirrhosis, has been reported in some cases of congenital hypofibrinogenemia. However, the details of FSD have not been studied. In this study, we attempted to elucidate the pathogenesis of FSD using model cells transfected with FSD gene mutations. In functional analysis of recombinant fibrinogen, we found abnormal fibrin polymerization reactions in FSD mutants. Furthermore, we did not obtain data suggesting a relationship with the endoplasmic reticulum stress response, and suspected the involvement of different mechanism in the accumulation of fibrinogen. We plan to continue analysis of fibrinogen functions in FSD mutants.

Free Research Field

血栓止血学

Academic Significance and Societal Importance of the Research Achievements

FSDの発症は先天性Fbg低下症患者において生命予後を左右する重大な合併症であり、その予防法・治療法の開発とそれに不可欠な病態メカニズムの解明は喫緊の課題である。本研究で、Fbgの重要なタンパク機能であるフィブリン重合反応において、FSD型変異Fbgにおける反応異常を明らかにした。FSDの病態解明に繋がる現象であるか、引き続き解析を予定している。