The role of large Mafs in kidney development

• 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
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 転写因子 / 大Maf / 大 Maf群転写因子 / ネフロン / 糸球体上皮細胞 / 近位尿細管 / 腎発生

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.

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。

Research Products

• [Journal Article] Anti-PM/Scl Antibody-positive Systemic Sclerosis Complicated by Multiple Organ Involvement (2021)
  • Author(s): Shimizu Tatsuya、Saito Chie、Watanabe Megumi、Ishii Ryota、Kawamura Tetsuya、Nagai Kei、Fujita Akiko、Kaneko Shuzo、Kai Hirayasu、Morito Naoki、Usui Joichi、Yokosawa Masahiro、Kondo Yuya、Inoue Sae、Okiyama Naoko、Yamagata Kunihiro
  • Journal Title: Internal Medicine Volume: 60 Issue: 7 Pages: 1101-1107
  • DOI: 10.2169/internalmedicine.5665-20
  • NAID: 130008014376
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2021-04-01
  • Peer Reviewed / Open Access
• [Journal Article] Anti-glomerular Basement Membrane Glomerulonephritis During the First Trimester of Pregnancy (2021)
  • Author(s): Kai Hirayasu、Usui Joichi、Tawara Takashi、Takahashi-Kobayashi Mayumi、Ishii Ryota、Tsunoda Ryoya、Fujita Akiko、Nagai Kei、Kaneko Shuzo、Morito Naoki、Saito Chie、Hamada Hiromi、Yamagata Kunihiro
  • Journal Title: Internal Medicine Volume: 60 Issue: 5 Pages: 765-770
  • DOI: 10.2169/internalmedicine.5722-20
  • NAID: 130007993548
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2021-03-01
  • Peer Reviewed
• [Journal Article] Transcription factor MafB in podocytes protects against the development of focal segmental glomerulosclerosis. (2020)
  • Author(s): Usui T, Morito N, Shawki HH, Sato Y, Tsukaguchi H, (20人略）, Takahashi S.
  • Journal Title: Kidney International Volume: in press Issue: 2 Pages: 391-403
  • DOI: 10.1016/j.kint.2020.02.038
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mice lacking core 1-derived O-glycan in podocytes develop transient proteinuria, resulting in focal segmental glomerulosclerosis (2020)
  • Author(s): Fuseya Sayaka、Suzuki Riku、Okada Risa、Hagiwara Kozue、Sato Takashi、Narimatsu Hisashi、Yokoi Hideki、Kasahara Masato、Usui Toshiaki、Morito Naoki、Yamagata Kunihiro、Kudo Takashi、Takahashi Satoru
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 523 Issue: 4 Pages: 1007-1013
  • DOI: 10.1016/j.bbrc.2020.01.033
  • Peer Reviewed
• [Journal Article] Literature review of allograft adenovirus nephritis and a case presenting as mass lesions in a transplanted kidney without symptoms of urinary tract infection or acute kidney injury (2020)
  • Author(s): Watanabe Megumi、Kaneko Shuzo、Usui Joichi、Takahashi Kazuhiro、Kawanishi Kunio、Takahashi‐Kobayashi Mayumi、Shimizu Tatsuya、Ishii Ryota、Tawara Takashi、Tsunoda Ryoya、Nagai Kei、Kawamura Tetsuya、Fujita Akiko、Kai Hirayasu、Morito Naoki、Saito Chie、Oda Tatsuya、Nagata Michio、Yamagata Kunihiro
  • Journal Title: Transplant Infectious Disease Volume: 23 Issue: 2
  • DOI: 10.1111/tid.13468
  • Peer Reviewed / Open Access
• [Journal Article] Mice Lacking Core 1-derived O-glycan in Podocytes Develop Transient Proteinuria, Resulting in Focal Segmental Glomerulosclerosis (2020)
  • Author(s): Sayaka Fuseya, Riku Suzuki, Risa Okada, Kozue Hagiwara, Takashi Sato, Hisashi Narimatsu , Hideki Yokoi, Masato Kasahara, Toshiaki Usui , Naoki Morito, Kunihiro Yamagata, Takashi Kudo , Satoru Takahashi
  • Journal Title: Biochem Biophys Res Commun Volume: 523 Issue: 2 Pages: 1007-1013
  • DOI: 10.1016/j.bbrc.2019.12.033
  • Peer Reviewed
• [Presentation] ANALYSIS OF A MOUSE MODEL FOR MCTO DUE TO THE MUTATION OF MAFB TRANSACTIVATION DOMAIN (2020)
  • Author(s): Usui Toshiaki; Morito Naoki; Takahashi Satoru; Yamagata Kunihiro
  • Organizer: Nephrology Virtual Congress 2020: 57th Congress
  • Int'l Joint Research