Role of pancreatic retinoid storage in pancreatic fibrosis and carcinogenesis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17396
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Gifu University
• Principal Investigator: Ozawa Noritaka 岐阜大学, 大学院医学系研究科, 招へい教員 (60761450)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 膵癌 / 膵線維化 / レチノイド / 膵星細胞

Outline of Final Research Achievements

The roles of retinoid storage in pancreatic stellate cells on pancreatic cancer and fibrosis were investigated. In lecithin:retinol acyltransferase (LRAT)-deficient mice, pancreatic retinoid storage measured by HPLC were significantly decreased compared to the control. In a model of pancreatitis and pancreatic fibrosis induced by caerulein injections, serum amylase and lipase were significantly higher and the mRNA expression level of fibrosis marker Timp1 was markedly elevated in the pancreas of LRAT-deficient mice. In addition, the pancreatic histology in mutant mice showed exacerbation of pancreatitis and significant increase of fibrous tissue. These results indicated LRAT deficiency exacerbates chronic pancreatitis and fibrosis, suggesting that differences in retinoid levels in pancreatic tissue might affect the pathology of the pancreas.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

レチニルエステル合成酵素(LRAT)欠損マウスの膵貯蔵レチノイドは有意に低値であったことから、この遺伝子改変マウスが膵レチノイド貯蔵欠如モデルとして適切であることが見出された。また、膵線維化モデルを用いた実験結果から、LRAT欠損すなわち膵レチノイド貯蔵の減少により慢性膵炎、膵線維化が増悪することが示された。
本研究結果は、膵貯蔵レチノイドが慢性膵炎および膵線維化を抑制する可能性を示しており、膵星細胞へのレチノイド補充もしくは脂肪滴喪失の阻害による、慢性膵炎・膵線維化および膵癌に対する治療法の開発につながると考えられる。