Elucidation of the molecular mechanisms underlying persistent pruritus in primary biliary cholangitis

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K06707
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Niigata University of Pharmacy and Medical and Life Sciences
• Principal Investigator: Maeda Takehiko 新潟薬科大学, 薬学部, 教授 (50271010)
• Co-Investigator(Kenkyū-buntansha): 長谷川 拓也 新潟薬科大学, 薬学部, 助手 (80813287) ; 川原 浩一 新潟薬科大学, 薬学部, 教授 (10347015)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Keywords: そう痒

Outline of Final Research Achievements

We made a mouse model of cholestatic pruritus (CP) to investigate the underlying molecular mechanisms. Bile duct ligation (BDL) was performed to establish a mouse model of CP. BDL led to increased serum levels of total bile acid, liver damage and spontaneous hind paw scratching in mice. Given the altered expression of gastrin-releasing peptide (GRP) in the skin and dorsal root ganglia (DRG) of the model mice, the study focused on functionally relevant TRP channels. In the DRG, TRPV4 expression increased, while in the skin, it decreased. CP model and TRPV4 knockout mice both revealed impaired skin moisture retention. These results suggest that skin TRPV4 may play a role in physiological skin barrier function and cholestatic pruritus.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

慢性肝疾患では胆汁の流出が停滞する胆汁うっ滞の症状が認められ、全身性かつ慢性のかゆみを伴うことがある。かゆみは生活動作や睡眠の障害を招き、QOLを著しく阻害するが、アレルギー性疾患と比較して、薬物療法は限られている。本研究成果は、難治性遷延性のそう痒症の発現機序解明に向けた基礎的資料となり得るものであり、慢性そう痒を伴う疾患の治療標的検索にも貢献するものである。