Foxc1/2 transcription factors and glomerulosclerosis

• Project/Area Number: 25461234
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Tokai University
• Principal Investigator: MOTOJIMA Masaru 東海大学, 医学部, 講師 (80468636)
• Co-Investigator(Kenkyū-buntansha): 松阪 泰二 東海大学, 医学部, 教授 (50317749)
• Co-Investigator(Renkei-kenkyūsha): ICHIKAWA Iekuni 東海大学, 医学部, 客員教授 (80317768) ; MIYAZAKI Yoichi 東京慈恵会医科大学, 医学部, 教授 (60266690)
• Research Collaborator: OHTSUKA Masato 東海大学, 医学部, 准教授 (90372945)
• Project Period (FY): 2013-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 糸球体硬化 / 転写因子 / フォークヘッド / ポドサイト / フォークヘッド転写因子 / 尿タンパク / ポドサイト傷害 / Foxc1 / Foxc2 / 腎発生

Outline of Final Research Achievements

Foxc1 and Foxc2 (Foxc1/2) are transcription factors involved in many biological processes including kidney development. Roles of Foxc1/2 in kidney were examined by conditional knockout mice.
Deletion of Foxc2 from early kidney development by Pax2-Cre resulted in kidney hypoplasia accompanied by glomerular cysts. Mice with an innate podocyte-specific deletion of Foxc1/2 by Nephrin-Cre developed massive proteinuria within 2 weeks after birth. Deletion of Foxc1/2 in adulthood by inducible-Cre resulted in development of massive proteinuria and glomerulosclerosis. Comprehensive gene expression analysis revealed that Foxc1/2 control genes necessary for podocyte function such as podocin and Cxcl12.
These results demonstrate critical roles for Foxc1/2 not only in kidney development but also podocyte maitenance.

Research Products

• [Int'l Joint Research] Northwestern University(米国)
• [Journal Article] Foxc1 and Foxc2 are necessary to maintain glomerular podocytes (2017)
  • Author(s): Masaru Motojima, Tsutomu Kume, Taiji Matsusaka
  • Journal Title: Exp Cell Res Volume: 352 Issue: 2 Pages: 265-272
  • DOI: 10.1016/j.yexcr.2017.02.016
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Characterization of Kidney and Skeleton Phenotypes of Mice Double Heterozygous for Foxc1 and Foxc2 (2016)
  • Author(s): Motojima M, Tanimoto S, Ohtsuka M, Matsusaka T, Kume T, Abe K
  • Journal Title: Cells Tissues Organs Volume: 201 Issue: 5 Pages: 380-389
  • DOI: 10.1159/000445027
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Conditional knockout of Foxc2 gene in kidney: efficient generation of conditional alleles of single-exon gene by double-selection system (2016)
  • Author(s): Motojima, Masaru; Ogiwara, Sanae; Matsusaka, Taiji; Kim, Sang Yong; Sagawa, Nobuho; Abe, Koichiro; Ohtsuka, Masato
  • Journal Title: Mamm Genome Volume: 27 Issue: 1-2 Pages: 62-69
  • DOI: 10.1007/s00335-015-9610-y
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Characterization of kidney and skeleton phenotypes of mice double-heterozygous for Foxc1 and Foxc2 (2016)
  • Author(s): Masaru Motojima, Sho Tanimoto, Masato Otsuka, Taiji Matsusaka, Tsutomu Kume , Koichiro Abe
  • Journal Title: Cells Tissues Organs Volume: In Press
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Foxc1 gene null mutation causes ectopic budding and kidney hypoplasia but not dysplasia. (2013)
  • Author(s): Komaki F,Miyazaki Y, Niimura F,Mtsusaka T, Ichikawa I,Motojima M .
  • Journal Title: Cells Tissues Organs. Volume: 198・1 Issue: 1 Pages: 22-27
  • DOI: 10.1159/000351291
  • Peer Reviewed
• [Presentation] Forkhead transcription factors, Foxc1 and Foxc2, regulate podocyte gene expression. (2016)
  • Author(s): Motojima M, Kume T, Matsusaka T
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-11-30
• [Presentation] Foxc1とFoxc2はポドサイトの成熟と維持に必須である (2016)
  • Author(s): 本島英、松阪泰二
  • Organizer: 第25回発達腎研究会
  • Place of Presentation: 聖路加臨床学術センター（東京都中央区）
  • Year and Date: 2016-08-27
• [Presentation] Forkhead transcription factors, Foxc1 and Foxc2, are required to maintain glomerular architecture. (2015)
  • Author(s): Masaru Motojima,Tsutomu Kume, Taiji Matsusaka
  • Organizer: 第38回日本分子生物学会年会／第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸国際展示場(兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] Foxc1 and Foxc2 cooperate in maintaining glomerular podocytes. (2015)
  • Author(s): Masaru Motojima, Tsutomu Kume, Taiji Matsusaka, Iekuni Ichikawa.
  • Organizer: Experimental Biology (EB) 2015
  • Place of Presentation: Boston
  • Year and Date: 2015-03-28 – 2015-04-01
• [Presentation] Efficient generation of conditional alleles in a single-exon gene locus by a double-selection system in mice. (2014)
  • Author(s): Masaru Motojima, Iekuni Ichikawa, Taiji Matsusaka, Masato Ohtsuka.
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Foxc1とFoxc2の腎発生における役割
  • Author(s): 本島英、市川家國
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸国際展示場