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Molecular mechanism on the formation and renewal of slit membranes of glomerular podocyte

Research Project

Project/Area Number 24591214
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionJuntendo University

Principal Investigator

KURIHARA HIDETAKE  順天堂大学, 医学部, 准教授 (80311976)

Co-Investigator(Kenkyū-buntansha) ICHIMURA Koichiro  順天堂大学, 医学部, 准教授 (10343485)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords腎臓学 / 足細胞 / 糸球体濾過 / 細胞接着 / ネフローゼ
Outline of Final Research Achievements

The slit diaphragm (SD) plays an important role in permeability barrier function. We have identified several molecules associated with the formation and renewal of SD. 1) To assess the function of MAGI-1, we analyzed the podocyte-specific MAGI-1 deficient mice and found that the deletion of MAGI-1 caused the decrease of SD molecules at the plasma membrane. In addition, exocytosis of nephrin molecule is inhibited by podocyte-specific deletion of aPKC. Data indicate that both molecules are associated with the turnover of SD. 2) We have found that myosin 1e is tightly associated with the tight junction which moves from the apex to the base of immature podocyte during the development. Myosin 1e is also involved in the SD formation. Recently, we have determined that KIF11 is tightly associated with tight junctions of renal epithelial cells in vivo and in vitro. Calcium switch experiment and silencing of KIF11 indicate that KIF11 is involved in the tight junction formation.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (30 results)

All 2015 2014 2013 2012

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 2 results,  Acknowledgement Compliant: 3 results) Presentation (14 results) (of which Invited: 3 results) Book (2 results)

  • [Journal Article] Podocyte injury-driven intracapillary plasminogen activator inhibitor type 1 accelerates podocyte loss via uPAR-mediated β1-integrin endocytosis.2015

    • Author(s)
      KobayashiN, Ueno T, Ohashi K, Yamashita H, Takahashi Y, Sakamoto K, Manabe S, Hara S, Takashima Y, Dan T, Pastan I, Miyata T, Kurihara H, Matsusaka T, Reiser J, Nagata M
    • Journal Title

      Am J Physiol Renal Physiol

      Volume: 308

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Afadin regulates RhoA/Rho-associated protein kinase signaling to control formation of actin stress fibers in kidney podocytes.2015

    • Author(s)
      Saito K,Shiino T,Kurihara H,Harita Y,Hattori S, Ohta Y
    • Journal Title

      Cytoskeleton

      Volume: 72 Issue: 3 Pages: 146-156

    • DOI

      10.1002/cm.21211

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Epithelial protein lost in neoplasm modulates platelet-derived growth factor-mediated adhesion and motility of mesangial cells2014

    • Author(s)
      Haruko Tsurumi, et. al
    • Journal Title

      Kidney International

      Volume: Epub Issue: 3 Pages: 548-557

    • DOI

      10.1038/ki.2014.85

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] aPKCλ maintains the integrity of the glomerular slit diaphragm through trafficking of nephrin to the cell surface.2014

    • Author(s)
      Satoh D, Hirose T, Harita Y, Daimon C, Harada T, Kurihara H, Yamashita A, Ohno S.
    • Journal Title

      J Biochem.

      Volume: 156(2) Issue: 2 Pages: 115-28

    • DOI

      10.1093/jb/mvu022

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Laminin alpha1 regulates age-related mesangial cell proliferation and mesangial matrix accumulation through the TGFbeta pathway.2014

    • Author(s)
      Ning L, Kurihara H, de Vega S, Ichikawa-Tomikawa N, Xu Z, Nonaka R, Yamada Y, Miner JH, Arikawa-Hirasawa E
    • Journal Title

      Am J Pathol

      Volume: 184 Issue: 6 Pages: 1683-1694

    • DOI

      10.1016/j.ajpath.2014.02.006

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Podocalyxin regulates pronephric glomerular development in zebrafish.2014

    • Author(s)
      Ichimura K, Nakamura T, Powell R, Kurihara H, Sakai T, Obara T.
    • Journal Title

      Physiological Report

      Volume: 1 Issue: 3

    • DOI

      10.1002/phy2.74

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mesenchymal stem cell transplantation to the mouse cochlea as a treatment for childhood sensorineural hearing loss.2013

    • Author(s)
      Kasagi H, Kuhara T, Okada H, Sueyoshi N, Kurihara H
    • Journal Title

      Int J Pediatr Otorhinolaryngol

      Volume: 77 Issue: 6 Pages: 936-942

    • DOI

      10.1016/j.ijporl.2013.03.011

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Myosin 1e is a component of the glomerular slit diaphragm complex that regulates actin reorganization during cell-cell contact formation in podocytes.2013

    • Author(s)
      Bi J, Chase S, Pellenz C, Kurihara H, Fanning A, Krendel M
    • Journal Title

      Am J Physiol Renal Physiol

      Volume: 305

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Podocyte expression of nonmuscle myosin heavy chain-IIA decreases in idiopathic nephrotic syndrome, especially in focal segmental glomerulosclerosis.2013

    • Author(s)
      Miura K, Kurihara H, Horita S, Chikamoto H, Hattori M, Harita Y, Tsurumi H, Kajiho Y, Sawada Y, Sasaki S, Igarashi T, Kunishima S, Sekine T.
    • Journal Title

      Nephrol Dial Transplant.

      Volume: 28 Issue: 12 Pages: 2993-3003

    • DOI

      10.1093/ndt/gft350

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] c-FLIP maintains tissue homeostasis by preventing apoptosis and programmed necrosis.2013

    • Author(s)
      Piao X
    • Journal Title

      Sci Signal

      Volume: ra93 Issue: 255

    • DOI

      10.1126/scisignal.2003558

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Significance of broad distribution of electron-dense deposits in patients with IgA nephropathy.2012

    • Author(s)
      Kusaba G, Ohsawa I, Ishii M, Inoshita H, Takagi M, Tanifuji C, Takahashi K, Nakamoto J, Yoshida M, Ohi H, Horikoshi S, Kurihara H, Tomino Y
    • Journal Title

      Med Mol Morphol

      Volume: 45 Issue: 1 Pages: 29-34

    • DOI

      10.1007/s00795-011-0538-3

    • NAID

      10030573625

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression of RASSF6 in kidney and the implication of RASSF6 and the Hippo pathway in the sorbitol-induced apoptosis in renal proximal tubular epithelial cells2012

    • Author(s)
      Withanage, K., Nakagawa, K., Ikeda, M., Kurihara, H., Kudo, T., Yang, Z., Sakane, A., Sasaki, T. and Hata, Y
    • Journal Title

      J. Biochem

      Volume: 152(1) Issue: 1 Pages: 111-119

    • DOI

      10.1093/jb/mvs056

    • NAID

      10031166119

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] SIRPα interacts with nephrin at the podocyte slit diaphragm.2012

    • Author(s)
      Kajiho Y, Harita Y, Kurihara H, Horita S, Matsunaga A, Tsurumi H, Kanda S, Sugawara N, Miura K, Sekine T, Hattori S, Hattori M, Igarashi T.
    • Journal Title

      FEBS J.

      Volume: 279 Issue: 17 Pages: 3010-3021

    • DOI

      10.1111/j.1742-4658.2012.08682.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A comparative analysis of glomerulus development in the pronephros of medaka and zebrafish2012

    • Author(s)
      Ichimura K, Bubenshchikova E, Powell R, Fukuyo Y, Nakamura T, Tran U, Oda S, Tanaka M, Wessely O, Kurihara H, Sakai T, Obara T
    • Journal Title

      PLoS One

      Volume: 7(9) Issue: 9 Pages: e45286-e45286

    • DOI

      10.1371/journal.pone.0045286

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 足細胞の細胞間接着を制御する新たな機構について2014

    • Author(s)
      栗原秀剛、坂井建雄
    • Organizer
      第46回日本臨床分子形態学会総会・学術集会
    • Place of Presentation
      東京
    • Year and Date
      2014-10-17 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 中間径線維タンパクネスチンの足細胞における発現とその機能的意義について2014

    • Author(s)
      栗原秀剛、坂井建雄
    • Organizer
      第57回日本腎臓学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-07-04 – 2014-07-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] 足細胞形態制御の分子機構2014

    • Author(s)
      栗原秀剛、坂井建雄
    • Organizer
      第119回日本解剖学会総会
    • Place of Presentation
      自治医大、栃木
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 腎臓における微小管モーター蛋白KIF11の局在について 第1報2014

    • Author(s)
      中村聡、岸龍馬、栗原秀剛、坂井建雄
    • Organizer
      第119回日本解剖学会総会
    • Place of Presentation
      自治医大、栃木
    • Related Report
      2013 Research-status Report
  • [Presentation] 腎臓における微小管モーター蛋白KIF11の局在について 第2報2014

    • Author(s)
      岸龍馬、中村聡、栗原秀剛、坂井建雄
    • Organizer
      第119回日本解剖学会総会
    • Place of Presentation
      自治医大、栃木
    • Related Report
      2013 Research-status Report
  • [Presentation] ポドサイトの形態変化に関わる細胞骨格系蛋白2013

    • Author(s)
      栗原秀剛
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] ポドサイトの突起形成におけるミオシンIIAの役割2013

    • Author(s)
      栗原秀剛、坂井建雄
    • Organizer
      第45回日本臨床分子形態学会総会
    • Place of Presentation
      福岡
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Heterologous expression of nestin is involved in cell-cell contact inhibition.2013

    • Author(s)
      Takizawa H, SakaiT, Kurihara H
    • Organizer
      53rd Annual Meeting of the American Society of Cell Biology
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] 神経幹細胞マーカーネスチンの足細胞における発現とその機能的意義2013

    • Author(s)
      瀧澤裕樹、長瀬駿介、栗原秀剛、坂井建雄
    • Organizer
      第118回日本解剖学会総会・全国学術集会
    • Place of Presentation
      高松
    • Related Report
      2012 Research-status Report
  • [Presentation] タイト結合蛋白MAGI-1の足細胞特異的ノックアウトマウスにおけるスリット膜分子の局在について2013

    • Author(s)
      長瀬駿介、瀧澤裕樹、栗原秀剛、坂井建雄
    • Organizer
      第118回日本解剖学会総会・全国学術集会
    • Place of Presentation
      高松
    • Related Report
      2012 Research-status Report
  • [Presentation] Using both medaka and zebrafish to study glomerulus development and slit diaphragms.2012

    • Author(s)
      Ichimura I, Bubenshchikova E, Fukuyo Y, Powell R, Hsu C, Tran U, Tanaka M, Wessey O, Kurihara H, Sakai T, Obara T
    • Organizer
      he 9th International Podocyte Conference
    • Place of Presentation
      Miami
    • Related Report
      2012 Research-status Report
  • [Presentation] EPLIN (Epithelial protein lost in neoplasm) interacts with paxillin and regulates mesangial migration.2012

    • Author(s)
      Tsurumi H, Harita Y, Kurihara H, Kajiho Y, Kanda S, Miura K, Sekine T, Hattori M, Igarashi T
    • Organizer
      American Society of Nephrology Renal week
    • Place of Presentation
      San Diego
    • Related Report
      2012 Research-status Report
  • [Presentation] Myosin IIA regulates the cellular architecture of podocyte.2012

    • Author(s)
      Kurihara, H, Sakai T
    • Organizer
      52nd Annual Meeting of the American Society of Cell Biology
    • Place of Presentation
      San Francisco
    • Related Report
      2012 Research-status Report
  • [Presentation] RacGAP因子FilGAPはAfadinと結合し、腎糸球体上皮細胞におけるアクチン細胞骨格形成を制御する2012

    • Author(s)
      椎野達大、斉藤康二、望月優加、栗原秀剛、張田豊、柴垣芳夫、服部成介、太田安隆
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Book] ジュンケイラ組織学 第3版2015

    • Author(s)
      栗原秀剛
    • Total Pages
      567
    • Publisher
      丸善
    • Related Report
      2014 Annual Research Report
  • [Book] 小児腎臓病学2012

    • Author(s)
      栗原秀剛
    • Total Pages
      460
    • Publisher
      診断と治療社
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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