Analysis of the functions of the PAR-aPKC complex in the regulation of the slit diaphragm proteins

2010 Fiscal Year Final Research Report

• Project/Area Number: 20790261
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Yokohama City University
• Principal Investigator: HIROSE Tomonori Yokohama City University, 医学部, 助教 (20381668)
• Project Period (FY): 2008 – 2010
• Keywords: シグナル伝達 / 疾患モデル動物 / 糸球体疾患 / 細胞極性 / 腎臓病

Research Abstract

The prevalence of end-stage renal disease (ESRD) in Japan have reached more than 290,000 by the end of 2009 and is still increasing by 10,000 a year. Although glomerular diseases cause about 80% of ESRD, the mechanisms of the pathophysiology and progression of glomerular diseases are still obscure. To resolve this situation, I established a new mouse line with a glomerular disease based on the disturbance in podocyte cell polarity and revealed a new aspect of the molecular mechanisms to maintain glomerular filtration function. These results would contribute to our understanding of the molecular pathophysiology of glomerular diseases and to the innovation of diagnostic techniques or medical interventions.

Research Products

• [Journal Article] Intrarenal suppression of angiotensin II type 1 receptor binding molecule in angiotensin II-infused mice. (2010)
  • Author(s): Wakui H, Tamura K, Matsuda M, Bai Y, Dejima T, Shigenaga AI, Masuda S, Azuma K, Maeda A, Hirose T, Ishigami T, Toya Y, Yabana M, Minamisawa S, Umemura S.
  • Journal Title: Am J Physiol Renal Physiol. 299(5) Pages: F991-1003
  • Peer Reviewed
• [Journal Article] Expression of angiotensin II type 1 receptor-interacting molecule in normal human kidney and IgA nephropathy. (2010)
  • Author(s): Masuda S, Tamura K, Wakui H, Maeda A, Dejima T, Hirose T, Toyoda M, Azuma K, Ohsawa M, Kanaoka T, Yanagi M, Yoshida S, Mitsuhashi H, Matsuda M, Ishigami T, Toya Y, Suzuki D, Nagashima Y, Umemura S.
  • Journal Title: Am J Physiol Renal Physiol. 299(4) Pages: F720-731
  • Peer Reviewed
• [Journal Article] ASPP2 Regulates Epithelial Cell Polarity through the PAR Complex. (2010)
  • Author(s): Cong W*, Hirose T*, Harita Y, Yamashita A, Mizuno K, Hirano H, Ohno S. (*equally contributed).
  • Journal Title: Curr Biol. 20(15) Pages: 1408-1414
  • Peer Reviewed
• [Journal Article] Expression of Toll-like receptor 9 in renal podocytes in childhood-onset active and inactive lupus nephritis. (2010)
  • Author(s): Machida H, Ito S, Hirose T, Takeshita F, Oshiro H, Nakamura T, Mori M, Inayama Y, Yan K, Kobayashi N, Yokota S.
  • Journal Title: Nephrol Dial Transplant. 25(8) Pages: 2530-2537
  • Peer Reviewed
• [Journal Article] An essential role of the universal polarity protein, aPKClambda, on the maintenance of podocyte slit diaphragms. (2009)
  • Author(s): Hirose T, Satoh D, Kurihara H, Kusaka C, Hirose H, Akimoto K, Matsusaka T, Ichikawa I, Noda T, Ohno S.
  • Journal Title: PLoS ONE. 4(1) Pages: e4194
  • Peer Reviewed
• [Journal Article] aPKC restricts the basolateral determinant PtdIns(3,4,5)P3 to the basal region. (2008)
  • Author(s): Takahama S, Hirose T, Ohno S.
  • Journal Title: Biochem Biophys Res Commun. 368(2) Pages: 249-255
  • Peer Reviewed
• [Presentation] Apoptosis-Stimulating Protein of p53 (ASPP2) is involved in the PAR Complex to Regulate Epithelial Cell Polarity. (2010)
  • Author(s): Cong W*, ○Hirose T*, Harita Y, Yamashita A, Mizuno K, Hirano H, Ohno S.(*equally contributed).
  • Organizer: 第62回日本細胞生物学会大会、ポスター発表
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-05-19
• [Presentation] Apoptosis-stimulating protein of p53 (ASPP2) regulate epithelial cell polarity through interacting with PAR-3. (2009)
  • Author(s): Cong W, ○Hirose T, Yamashita A, Mizuno K, Harita Y, Kurata R, Hirano H, Ohno S.
  • Organizer: 第32回日本分子生物学会年会、ワークショップ4W2
  • Place of Presentation: 横浜(口頭発表)
  • Year and Date: 2009-12-12
• [Presentation] 腎糸球体ポドサイトの糸球体濾過膜維持の新しい分子機構:細胞極性制御系aPKC-PAR系の役割 (2009)
  • Author(s): 廣瀬智威、佐藤大輔、栗原秀剛、日下智保、廣瀬博子、秋本和憲、松阪泰二、市川家國、伊藤秀一、野田哲生、大野茂男
  • Organizer: 第52回日本腎臓学会学術総会
  • Place of Presentation: 横浜(一般演題:口演)
  • Year and Date: 2009-06-04
• [Presentation] A New Mouse Model of Focal Segmental Glomerulosclerosis with Defective Cell Polarity in Podocytes. (2009)
  • Author(s): ○Hirose T, Satoh D, Kurihara H, Kusaka C, Hirose H, Akimoto K, Matsusaka T, Ichikawa I, Noda T, Ohno S.
  • Organizer: 第2回横浜市立大学・米国食品医薬品庁共催 国際学術ワークショップ
  • Place of Presentation: 横浜
  • Year and Date: 2009-03-04
• [Presentation] 腎糸球体ポドサイトの糸球体濾過膜維持における新しい分子機構 (2009)
  • Author(s): 廣瀬智威
  • Organizer: お茶の水がん学アカデミア
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2009-02-23
• [Presentation] A cell polarity protein, aPKCλ, plays a critical role on the maintenance of podocyte slit diaphragm. (2008)
  • Author(s): ○廣瀬智威、佐藤大輔、栗原秀剛、松阪泰二、秋本和憲、市川家國、野田哲生、大野茂男
  • Organizer: The 7th International Podocyte Meeting
  • Place of Presentation: Toronto
  • Year and Date: 20080604-20080606
• [Presentation] 細胞極性制御蛋白質aPKCλは、特殊な細胞間接着装置である腎糸球体ポドサイトの糸球体濾過膜の維持に必須の役割を担う (2008)
  • Author(s): ○廣瀬智威、佐藤大輔、栗原秀剛、日下智保、廣瀬博子、秋本和憲、松阪泰二、市川家國、野田哲生、大野茂男
  • Organizer: BMB2008-第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会、シンポジウム
  • Place of Presentation: 神戸(招待講演)
  • Year and Date: 2008-12-09
• [Remarks] McCarthy, N., Research Highlight.Cell Polarity : ASPP2 gets a polarity complex.Nat Rev Cancer, 10:528.(August 2010)
• [Remarks] Holzman, B.H., Garg P., In This issue.Initial Insight on the Determinants of Podocyte Polarity.J Am Soc Nephrol, 20: 683-685.(April 2009)
• [Remarks] 読売新聞 平成21年2月22日
• [Remarks] 科学新聞 平成21年1月23日
• [Remarks]
  • URL: http://www-user.yokohama-cu.ac.jp/~ohnos/news/News100708.html
• [Remarks]
  • URL: http://www-user.yokohama-cu.ac.jp/~ohnos/news/News090119.html