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

• Project/Area Number: 24591214
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Juntendo 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: ¥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.

Research Products

• [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
  • 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
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Epithelial protein lost in neoplasm modulates platelet-derived growth factor-mediated adhesion and motility of mesangial cells (2014)
  • Author(s): Haruko Tsurumi, et. al
  • Journal Title: Kidney International Volume: Epub Issue: 3 Pages: 548-557
  • DOI: 10.1038/ki.2014.85
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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 cells (2012)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] A comparative analysis of glomerulus development in the pronephros of medaka and zebrafish (2012)
  • 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
  • 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
• [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
• [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
  • 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
• [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
• [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
  • 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
  • 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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [Book] 小児腎臓病学 (2012)
  • Author(s): 栗原秀剛
  • Total Pages: 460
  • Publisher: 診断と治療社