A role of SHPS-1/CD47 signaling pathway in the glomerular barrier function

• Project/Area Number: 20590945
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Gunma University
• Principal Investigator: NOJIMA Yoshihisa Gunma University, 大学院・医学系研究科, 教授 (90201699)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: SHPS-1 / SIRP-a / 糸球体バリアー機能 / チロシン脱リン酸化 / 情報伝達 / CD47 / SIRP-α

Research Abstract

SHPS-1 (SIRP-α) is a transmembrane protein having ITIM motif in its cytoplasmic domain. When the ITIM motif in SHPS-1 is tyrosine-phospholylated by a variety of stimuli, SHPS-1 binds tyrosine phosphatases, SHP-1 or SHP-2, which dephospholylates neighboring proteins and transmits signals to downstream. In this study, we have shown that SHPS-1 is expressed on podocytes and plays a significant role in structure and function of podocytes by using mutant mice expressing SHPS-1 with a deleted cytoplasmic domain. The results strongly suggest that the tyrosine-dephosphorylation system is involved in maintaining the barrier function of glomerulus.

Research Products

• [Journal Article] Effects of proteasome inhibitors on rat renal fibrosis in vitro and in vivo. (2011)
  • Author(s): Sakairi T, Hiromura K, Takahashi S, Hamatani H, Takeuchi S, Tomioka M, Maeshima A, Kuroiwa T, Nojima Y
  • Journal Title: Nephrology (Carlton). 16(1) Pages: 76-86
  • Peer Reviewed
• [Journal Article] Nestin is a novel marker for renal tubulointerstitial injury in immunoglobulin A nephropathy. (2010)
  • Author(s): Tomioka M, Hiromura K, Sakairi T, Takeuchi S, Maeshima A, Kaneko Y, Kuroiwa T, Takeuchi T, Nojima Y.
  • Journal Title: Nephrology (Carlton). 15 Pages: 568-74
  • Peer Reviewed
• [Journal Article] Proteomic analysis identifies insulin-like growth factor binding protein-related protein 1 as a podocyte product. (2010)
  • Author(s): Matsumoto T, Hess S, Kajiyama H, Sakairi T, Saleem MA, Mathieson P, Nojima Y, Kopp JB.
  • Journal Title: Am J Physiol Renal Physiol. 299(4)
  • Peer Reviewed
• [Journal Article] The Immunosuppressive Drug Mizoribine Directly Prevents Podocyte Injury in Puromycin Aminonucleoside Nephrosis. (2010)
  • Author(s): Takeuchi S, Hiromura K, Tomioka M, Takahashi S, Sakairi T, Maeshima A, Kaneko Y, Kuroiwa T, Nojima Y.
  • Journal Title: Nephron Exp Nephrol. 21;116(1)
  • Peer Reviewed
• [Journal Article] Nestin is a novel marker for renal tubulointerstitial injury in immunoelobulin A nenhronathv. (2010)
  • Author(s): Tomioka M, Hiromura K, N oiima Y, et al
  • Journal Title: Nephrology (Carlton). Volume: 15 Pages: 568-574
  • Peer Reviewed
• [Journal Article] Proteomic analysis identifies insulin-like growth factor bindin protein-related protein 1 as a nodocvte product. (2010)
  • Author(s): Matsumoto T, Nojima Y, et al
  • Journal Title: Am J Physiol Renal Physiol. Volume: 299
  • Peer Reviewed
• [Journal Article] The Immunosuppressive Drug Mizoribine Directly Prevents Podocyte Injury in Puromycin Aminonucleoside Nephrosis. (2010)
  • Author(s): Takeuchi S, Hiromura K, N ojima Y., et al
  • Journal Title: Nephron Exp Nephrol. Volume: 116
  • Peer Reviewed
• [Journal Article] Fluvastatin prevents podocyte injury in a murine model of HIV-associated nephropathy. (2009)
  • Author(s): Sakurai N, Kuroiwa T, Ikeuchi H, Hiramatsu N, Takeuchi S, Tomioka M, Shigehara T, Maeshima A, Kaneko Y, Hiromura K, Kopp JB, Nojima Y.
  • Journal Title: Nephrol Dial Transplant. 24(8) Pages: 2378-83
  • Peer Reviewed
• [Journal Article] Fluvastatin prevents podocyte injury in a murine model of HIV-associated nephropathy. (2009)
  • Author(s): Sakurai N, Kuroiwa T, Ikeuchi H, Hiramatsu N, Takeuchi S, Tomioka M, Shigehara T, Maeshima A, Kaneko Y, Hiromura K, Kopp JB, Nojima Y.
  • Journal Title: Nephrol Dial Transplant. 24 Pages: 2378-83
  • Peer Reviewed
• [Journal Article] Resistance to collagen-induced arthritis in SHPS-1 mutant mice. (2008)
  • Author(s): Okuzawa C, Kaneko Y, Murata Y, Miyake A, Saito Y, Okajo J, Tomizawa T, Kaneko Y, Okazawa H, Ohnishi H, Matozaki T, Nojima Y.
  • Journal Title: Biochem Biophys Res Commun 37 Pages: 561-566
  • Peer Reviewed
• [Presentation] Efficacy of Low-Dose Tacrolimus (TAC) in Induction Therapy of Lupus Nephritis (LN) (2010)
  • Author(s): Takahashi T, Hiromura K, Nojima Y, et al.
  • Organizer: 第43回アメリカ腎臓学会
  • Place of Presentation: デンバー(米国)
  • Year and Date: 2010-11-20
• [Presentation] The Role of SIRPα (SHPS-1) in Experimental Diabetic Nephropathy. (2010)
  • Author(s): Takahashi T, Hiromura K, Nojima Y, et al.
  • Organizer: 第43回アメリカ腎臓学会
  • Place of Presentation: デンバー(米国)
  • Year and Date: 2010-11-19
• [Presentation] The Role of SIRPα (SHPS-1) in Experimental Diabetic Nephr opathy. (2010)
  • Author(s): Takahashi T, Hiromura K, Noiima Y, et al.
  • Organizer: 第43回アメリカ腎臓学会
  • Place of Presentation: デンバー(米国)
  • Year and Date: 2010-11-19
• [Presentation] Tubulointerstitial nestin expression as a predictive marker for renal prognosis in IgA nephropathy. (2010)
  • Author(s): Tomioka M, Hiromura K, Nojima Y, et al.
  • Organizer: 国際腎臓学会NEXUS京都シンポジウム
  • Place of Presentation: 京都国際会議場(京都)
  • Year and Date: 2010-04-17
• [Presentation] The Role of SIRPα in Podocyte Structure and Function. (2010)
  • Author(s): Tomioka M, Hiromura K, Nojima Y
  • Organizer: 国際腎臓学会NEXUS 京都シンポジウム
  • Place of Presentation: 京都国際会議場(京都)
  • Year and Date: 2010-04-16
• [Presentation] SIRPαは糸球体上皮細胞の形態と蛋白尿制御に関与する (2009)
  • Author(s): 富岡麻衣、廣村桂樹、高橋哲史、前嶋明人、金子和光、黒岩卓、青木武生、高田邦昭、大西浩史、的崎尚、野島美久
  • Organizer: 第10回腎不全病態治療研究会
  • Place of Presentation: 東京
  • Year and Date: 2009-12-12
• [Presentation] SIRP α (SHPS-1) Signaling Pathway Is Involved in Podocyte Structure and Function. (2009)
  • Author(s): Tomioka M, Hiromura K, Nojima Y, et al.
  • Organizer: 第42回アメリカ腎臓学会
  • Place of Presentation: サンディエゴ(米国)
  • Year and Date: 2009-10-29
• [Presentation] SIRPα(SHPS-1)Signaling Pathway Is Involved in Podocyte Structure and Function (2009)
  • Author(s): Tomioka M, Hiromura K, Takahashi S, Takeuchi S, Maeshima A, Kuroiwa T, Kaneko Y, Saito Y, Ohnishi Y, Matozaki T, Aoki T, Takata T, Nojima Y
  • Organizer: 第42回アメリカ腎臓学会
  • Place of Presentation: 米国 サンディゴ
  • Year and Date: 2009-10-29
• [Presentation] 糖尿病性腎症におけるSHPS-1シグナル経路に関する検討 (2009)
  • Author(s): 高橋哲史, 廣村桂樹, 富岡麻衣, 竹内茂, 前嶋明人, 黒岩卓, 金子和光, 大西浩史, 的崎尚, 野島美久
  • Organizer: 第52回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-06-04
• [Presentation] Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase Substrate 1(SHPS-1) Protects Against Podocyte Injury (2008)
  • Author(s): Tomioka M, Hiromura K, Takeuchi, Tetsushi S, Takahashi T, Okuzawa C, Maeshima A, Kuroiwa T, Kaneko Y, Saito Y, Ohnishi Hi, Matozaki T, Nojima Y
  • Organizer: The Annual Meeting of American Society of Nephrology
  • Place of Presentation: Philaderphia, USA
  • Year and Date: 2008-11-06