Role of in glomerular injury

• Project/Area Number: 18590885
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Niigata University
• Principal Investigator: TAKEDA Tetsuro Niigata University, Hospital, Assistant professor (10361924)
• Co-Investigator(Kenkyū-buntansha): SAITO Akihiko Niigata University, Graduate School of Medical and Dental Sciences, Professor (80293207)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
• Keywords: Renal glomerulus / Podocyte / protein-protein interaction / Sugar transferase / Angiotensin II / Honeycomb-patterned film / Altered glycation / Adaptor protein

Research Abstract

We have previously demonstrated that an anti-adhesin molecule, podocalyxin binds to the adaptor proteins and that the interaction is important to maintain the unique organization of podocyte structure. In this research project, we focused on altered glycation of podocalyxin that should affect glomerular adhesion, indicating a marker of severe kidney diseases. We investigated what kind of sugar transferases are specifically expressed in podocyte and carried out 2-D SDS-PAGE to detect the altered glycation of podocalyxin. Also, we tested podocyte-specific mRNA expression whether novel material of substratum, honeycomb patterned film provides suitable circumference for podocyte culture.
1. We found that two unique sugar transferases (glycoprotein-N-acetylgalactosamine-3-13-galactosyltransferase, C1Gal-t-1, UDP-G1cNAc 2-epimerase, GNE) are expressed in podocyte in vitro and in vivo by RT-PCR.
2. Podocyte-specific mRNA (nephrin, CD2AP, podocalyxin) expression was increased in podocyte cultured on honeycomb patterned-film. Multi-layered cells cultured on this film were observed by scanning electron microscopy.
3. We also found that the interaction between podocalyxin and adaptor proteins (NHERF2 and ezrin) in podocyte cell lines was reduced in proportion to the angiotensin II concentration.
4. We failed to analyze sugar chains of purified podocalyxin, because to technical problems.

Research Products

• [Journal Article] Functional characterization of a novel missense CLCN5 mutation causing alterations in proximal tubular endocytic machinery in Dent' s disease (2007)
  • Author(s): Tanuma A
  • Journal Title: Nephron Physiol 107 Pages: 87-97
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Megalin-mediated endocytosis of cystatin C in proximal tubule cells (2007)
  • Author(s): Kaseda R
  • Journal Title: Biochemical and Biophysical Research Communications 357 Pages: 1130-1134
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Functional Characterization of a Novel Missense CLCN5 Mutation Causing Alterations in Proximal Tubular Endocytic Machinery in Dent's Disease (2007)
  • Author(s): A, Tanuma, H, Sato, T, Takeda, M, Hosojima, H, Obayashi, H, Hama, N, Iino, K, Hosaka, R, Kaseda, N, Imai, M, Ueno, M, Yamazaki, K, Sakimura, F, Gejyo, A, Saito
  • Journal Title: Nephron Physiol 107(4) Pages: 87-97
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Megalin-mediated endocytosis of cystatin C in proximal tubule cells (2007)
  • Author(s): R, Kaseda, N, Iino, M, Hosojima, T, Takeda, K, Hosaka, A, Kobayashi, K, Yamamoto, A, Suzuki, A, Kasai, Y, Suzuki, F, Gejyo, A, Saito
  • Journal Title: Biochemical and Biophysical Research Communications 357(4) Pages: 1130-1134
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Role of proximal tubule cells in the intrarenal renin-angiotensin system.(edited by F Gejyo, T Oite, Y Suzuki, M Uchiyama, F Shimizu, K Takahashi, T Yamamoto, Niigata Symposium of Nephrology Organizing Committee Niigata University) (2007)
  • Author(s): A, Saito
  • Journal Title: Proceedings of the 21st Niigata Symposium of Nephrology. Recent advances and new insight into the Renin-Angiotensin-Aldosterone system in the Kidney(Koko-Do・Niigata) Pages: 24-28
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Functional characterization of a novel missense CLCN5 mutation causing alterations in proximal tubular endocytic machinery in Dent's disease. (2007)
  • Author(s): A Tanum, H Sato, T Takeda, ., F Gejyo, A Saito
  • Journal Title: Nephron Physiol 107 Pages: 87-97
  • Peer Reviewed
• [Journal Article] Megalin-mediated endocytosis of cystatin C in proximal tubule cells. (2007)
  • Author(s): R Kaseda, N Iino, M Hosojima, T Takeda, ., F Gejyo, A Saito
  • Journal Title: Biochemical and Biophysical Research Communications 357 Pages: 1130-1134
  • Peer Reviewed
• [Journal Article] レプチンと腎疾患 (2007)
  • Author(s): 飯野則昭, 濱ひとみ, 竹田徹朗, 下条文武, 斎藤亮彦
  • Journal Title: Annual Review腎臓 2007巻 Pages: 20-23
• [Journal Article] Para-capillary electron-dense deposits reduce glomerular filtration in patients with primary glomerular diseases (2006)
  • Author(s): Fukase S
  • Journal Title: Clinical and Experimental Nephrology 10 Pages: 33-39
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Para-capillary electron-dense deposits reduce glomerular filtration in patients with primary glomerular diseases (2006)
  • Author(s): S, Fukase, JJ, Kazama, H, Mori, S, Iguchi, T, Takeda, M, Ueno, S, Nishi, I, Narita, F, Gejyo
  • Journal Title: Clinical and Experimental Nephrology 10(1) Pages: 33-39
  • NAID: 10017320238
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 向精神薬による腎障害 (2006)
  • Author(s): 竹田徹朗, 成田一衛, 下条文武
  • Journal Title: ICUとCCU 30巻・10号 Pages: 1013-1020
• [Journal Article] メガリン・キュプリン-尿細管での蛋白再吸収における役割 (2006)
  • Author(s): 竹田徹朗, 斎藤亮彦, 下条文武
  • Journal Title: 日本臨床 64巻増刊2 Pages: 332-338
• [Journal Article] Para-Capillary electron-dense deposits reduce glomerular filtration in patients with primary glomerular diseases (2006)
  • Author(s): Fukase S, Kazama JJ, Mori H, Iguchi S, Takeda T, Ueno M, Nishi S, Narita I, Gejyo F
  • Journal Title: Clinical and Experimental Nephrology 10 Pages: 33-39
  • NAID: 10017320238
• [Presentation] Angiotensin II and insulin-mediated signaling cross-talks for the expression of megalin in cultured proximal tubule cells (2007)
  • Author(s): Hosojima M
  • Organizer: The 40th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: San Francisco, CA, USA
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] TJ Thekkumkara, Tetsuro Takeda, Fumitake Gejyo, Akihiko Saito: Angiotensin II and insulin-mediated signaling cross-talks for the expression of megalin in cultured proximal tubule cells (2007)
  • Author(s): M, Hosojima, N, Iino, A, Kobayashi, R, Kaseda, A, Nishiyama
  • Organizer: The 40th Annual Meeting of the American Society of Nephrology/Renal Week 2007
  • Place of Presentation: San Francisco, CA, USA
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Long-term renal prognosis of Japanese patients with obesity/metabolic syndrome related nephropathy (2006)
  • Author(s): A, Saito, M, Ueno, M, Hosojima, R, Kaseda, K, Hosaka, N, Iino, T, Takeda, S, Nishi, Y, Suzuki, F, Gejyo
  • Organizer: The 39th Annual Meeting of the American Society of Nephrology/Renal Week 2006
  • Place of Presentation: San Diego, CA, USA
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Proceedings of the 21st Niigata Symposium oh Nephro logy: Recent advances and new insight into the Renin-Angiotensin-Aldsterone system in the Kidney (2007)
  • Author(s): A Saito
  • Publisher: Koko-Do・Niigata
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Proceedings of the 21st Niigata Symposium oh Nephrology: Recent advances and new insight into the Renin-Angiotensin-Aldsteron system in the Kidney (2007)
  • Author(s): A Saito (edited by F Gejyo, T Oite, M Uchiyama, F Shimizu, K Takahashi, T Yamamoto)
  • Total Pages: 5
  • Publisher: Koko-Do・Niigata