The role of MafB in CKD.

• Project/Area Number: 15K09241
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: University of Tsukuba
• Principal Investigator: Morito Naoki 筑波大学, 医学医療系, 講師 (70463825)
• Research Collaborator: USUI TOSHIAKI 筑波大学, 医学医療系, 講師
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 糸球体上皮細胞 / 転写因子 / 巣状糸球体硬化症

Outline of Final Research Achievements

Analysis of MafB deficient (MafB -/-) mice revealed that MafB is essential for podocyte differentiation and its foot process formation. However, the role of MafB in adult kidneys was not well known. Because MafB -/- mice die during the perinatal period, we used MafB heterozygote (MafB +/-) mice in this study.
We found that MafB +/- mice developed overt albuminuria at 50 week-old of age. By the electron microscopy analysis, we observed podocyte foot process effacement in MafB +/- mice. RT-PCR analysis revealed the Nephrin and Podocin glomerular expressions were decreased in MafB +/- mice compared to wild-type animals. We exploited transgenic mice expressing MafB in podocytes using Nephrin promoter (NPHS1 -MafB TG mice). We found that the NPHS1 MafB transgene successfully restored MafB mice to normal albuminuria at 50 week-old of age.
Conclusions: MafB is essential for the maintenance of podocytes. MafB could be a therapeutic target in chronic kidney disease.

Research Products

• [Journal Article] Transcription factor MafB may play an important role in secondary hyperparathyroidism. (2018)
  • Author(s): Morito N, Yoh K, Usui T, Oishi H, Ojima M, Fujita A, Koshida R, Shawki HH, Hamada M, Muratani M, Yamagata K, Takahashi S.
  • Journal Title: Kidney International Volume: 93 Issue: 1 Pages: 54-68
  • DOI: 10.1016/j.kint.2017.06.023
  • Peer Reviewed / Int'l Joint Research
• [Presentation] MAFB IS ESSENTIAL FOR THE MAINTENANCE OF PODOCYTES IN BOTH MICE AND HUMANS. (2017)
  • Author(s): 臼井俊明、森戸直記
  • Organizer: 第54回ヨーロッパ腎臓学会 マドリード（スペイン）2017年6月3－6日
  • Int'l Joint Research
• [Presentation] 転写因子Mafbによる副甲状腺ホルモンの制御 (2016)
  • Author(s): 森戸 直記
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2016-06-17
• [Presentation] MAFB MUTANT SHOWS PODOCYTE INJURY WITH AGING (2016)
  • Author(s): Naoki Morito
  • Organizer: 第53回ヨーロッパ腎臓学会
  • Place of Presentation: Messe Wien Exhibition & Congress Centre(ウィーン、オーストリア）
  • Year and Date: 2016-05-21
  • Int'l Joint Research
• [Presentation] 転写因子Mafbのハプロ不全はpodocyte障害をもたらす (2015)
  • Author(s): 森戸直記
  • Organizer: 日本腎臓学会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2015-06-05