Novel transgenic mice, Erythropoietin-CreERT2 mice, label unique subpopulations of renal fibroblasts

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09259
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kyoto University
• Principal Investigator: Endo Shuichiro 京都大学, 医学研究科, 助教 (80533380)
• Co-Investigator(Kenkyū-buntansha): 柳田 素子 京都大学, 医学研究科, 教授 (70378769)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 腎線維化 / 腎性貧血 / 線維芽細胞

Outline of Final Research Achievements

Erythropoietin (Epo) is produced by a small subpopulation of resident fibroblasts in the healthy kidney and renal anemia is on of the complications of chronic kidney disease (CKD). It has not been fully elucidated whether Epo-producing cells are the distinct and specialized subpopulation of resident fibroblasts, or all resident fibroblasts possess the capacity to produce Epo. Here we generated a novel mouse strain, EpoCreERT2/+ mice, which label Epo-producing cells at the desired time points, and examined the behaviors of Epo-producing cells. Utilizing this mouse strain, we showed that Epo-producing cells maintained Epo-producing ability and proliferated during fibrosis, indicating that Epo-producing cells are the distinct population of renal fibroblasts. Further analysis of the Epo-producing cell population will lead to new therapeutic approach to renal anemia.

Free Research Field

腎臓病学

Academic Significance and Societal Importance of the Research Achievements

新規遺伝子組換えマウスEpo-CreERT2マウスを作製し、任意の時点でEpo産生細胞を標識することに成功した。このマウスを用いて、成体腎におけるEpo産生細胞が線維化腎でmyofibroblastに形質転換することを初めて証明した。さらに特定の細胞が繰り返しEpo産生を担う可能性やEpo産生細胞が他の線維芽細胞と比べて増殖しやすい可能性が示唆され、Epo産生細胞は線維芽細胞における特殊な細胞集団である可能性が示唆された。今後、Epo産生細胞集団の解析を進め、腎性貧血の機序の解明と新規治療法開発に繋げたい。