The role of large Mafs in kidney development

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08230
• 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: University of Tsukuba
• Principal Investigator: Morito Naoki 筑波大学, 医学医療系, 講師 (70463825)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 転写因子 / 大Maf

Outline of Final Research Achievements

In kidney development, Nephron progenitor cells give rise to multiple cell types of the nephron, including podocytes, proximal and distal tubules. We previously reported MafB is essential for podocyte development. Since MafB knockout (KO) mice died out at perinatal period, we analyzed renal development at Embryo 18.5 days (E18.5).
We found podocyte foot process effacement was observed in KO kidneys. Proximal tubule cells（LTL；Lotus tetragonolobus lectin-positive）was significantly decreased in KO kidneys compared with WT (wild-type) ones. Meanwhile, we could not find any differences in distal tubule cells（Slc12a3-positive）between KO and WT kidneys. These observations were resembled to Notch2-deficient kidneys. RT-PCR analysis revealed Notch2 expression was decreased in MafB knockout kidneys compared with WT ones. MafB may play an important role in podocytes and proximal tubules development.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

大Maf群転写因子のネフロン発生と分化における機能については、糸球体上皮細胞についての報告はあるものの近位尿細管、遠位尿細管発生に関するものはほとんどない。MafBは糸球体上皮細胞と近位尿細管細胞の分化に必須であるが、遠位尿細管細胞ではそうではないこと、c-Mafは近位尿細管の発生には必須ではないことを示した。また、ネフロン前駆細胞の大Maf群転写因子の発現パターンを制御することで、将来的な再生医療に生かすことができる可能性がある。