Research for kidney repair mechanisms in acute kidney injury using disease specific iPS cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08699
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Kanazawa Medical University
• Principal Investigator: FURUICHI Kengo 金沢医科大学, 医学部, 教授 (50432125)
• Co-Investigator(Kenkyū-buntansha): 和田 隆志 金沢大学, その他部局, その他 (40334784)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 急性腎障害 / 疾患特異的iPS細胞 / 腎修復 / CAGE解析

Outline of Final Research Achievements

This study aims to elucidate the repair mechanism. And the goal of this study is preventing the transition of acute kidney injury to chronic kidney disease. Disease-specific iPS cells were created from renal coloboma syndrome cases with Pax2 gene mutation that play an important role in kidney development. The cells were induced into kidney lineage cells. From the cells, we evaluate gene expression with the CAGE method and Chip-Seq analysis, and identified candidate molecules that are considered to be involved in kidney repair after the injury. The candidate genes (17 genes with 28 promoter regions) were confirmed from the open database of mouse fetal kidney. Using samples such as the mouse ischemia-reperfusion model in kidney, the three genes (PBX1, POSTN, and ITGA9) were finally identified as kidney repair factors regulated by PAX2 gene.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

腎再生や修復機序の解明は、これまでも試みられてきたが、腎発生との関連の研究は限られていた。今回、非常に稀少な遺伝性疾患であるPax2遺伝子変異を伴った腎コロボーマ症候群症例の疾患特異的iPS細胞を腎系譜細胞へ分化させ、その関連分子を同定できたことは、本分野における重要なマイルストンと考える(Sci Rep. 2021;11:9123. )。今回同定された腎再生・修復に関わると考えられる候補分子には、これまで腎障害や修復への関与は報告されていないものも含まれている。直接的な修復に果たす意義は更なる解析が必要だが、バイオマーカーや治療薬開発に向けた重要な足がかりになる可能性があると考える。