The Origin of Collagen-producing Myofibroblasts in Pancreatic Fibrosis

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670575
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyoto University
• Principal Investigator: TAURA Kojiro 京都大学, 医学(系)研究科(研究院), 講師 (80378629)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 慢性膵炎 / 膵線維化 / 膵星細胞 / 肝星細胞 / ビタミンA / コラーゲン

Outline of Final Research Achievements

We aimed to pursue the origin of collagen-producing cells in pancreatic fibrosis by using transgenic mice expressing GFP under collagen α1(I) promoter. Pancreatic fibrosis was induced by cerulein. GFP-positive cells were seen along fibrotic septa but only a small minority of the cells were positive for glial fibrillary acidic protein (GFAP), a specific marker of PSCs.
The flowcytometry of isolated pancreatic cells from cerulein-treated mice showed GFAP-positive cells accounted for only 20% of GFP-positive cells. PSCs had lipid droplets, however, unlike HSCs, they lacked vitamin A autofluorescence. Liquid chromatography mass spectrometry analysis of the cell extract revealed PSCs contained only trace amounts of retinyl palmitate. The mRNA expression of Lrat, an enzyme necessary to esterify retinol, was much lower than that of HSCs. In conclusion, our study suggested the presence of collagen-producing cells other than PSCs and showed different characteristics between PSCs and HSCs.

Free Research Field

肝胆膵外科　移植外科