Roles of Girdin in organ fibrosis and cancer associated fibrosis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07042
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Fujita Health University (2019-2020); Nagoya University (2018)
• Principal Investigator: Asai Naoya 藤田医科大学, 医学部, 教授 (80273233)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 臓器線維症 / 癌関連線維芽細胞 / 間葉系幹細胞 / 遺伝子改変動物 / 細胞運動

Outline of Final Research Achievements

Fibrosis can affect any organs and cancers, which lead poor prognosis in patients. To reveal mechanisms of fibrosis, we studied on Girdin and Meflin. With two mutant mice of Girdin S1416A and Girdin Y1764/1798F, we checked the importance of Girdin phosphorylation in fibrosis. Both Girdin mutant mice showed no significant impact of fibrotic status in organ fibrosis models in lung, liver and cancers. Meflin is a novel mesenchymal stem cell marker, and Meflin deficient mice show skin fibrosis, which is similar to systemic sclerosis in humans. By lineage trace experiment, we identified new subpopulation of kidney mesenchymal cells, which express Meflin and can differentiate into renin producing cells. Meflin-positive mesenchymal cells in kidney have important roles in kidney fibrosis, and patients of IgA nephropathy with many Meflin-positive cells show poor prognosis.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

本研究により、Meflin欠損マウスにはヒト疾患の強皮症に類似した皮膚線維症の病態が生じることが判明したことから、疾患モデルとしての有効利用が期待される。
腎臓においてMeflin陽性細胞は血圧を制御するレニン産生細胞への分化を介して腎性高血圧へ関与すること、Mefliny陽性細胞の数がIgA腎症の予後不良因子となるとともに、腎間質線維症への関与することから、Meflin遺伝子が腎疾患における新たな治療ターゲットとなる可能性が期待される。