The elucidation of the role of ABC transporters in retinal angiogenesis

• Project/Area Number: 22791660
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Ophthalmology
• Research Institution: Kobe University
• Principal Investigator: KUSUHARA Sentaro 神戸大学, 大学院・医学研究科, 助教 (40437463)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: ABCトランスポーター / MRP4 / 血管新生 / 網膜血管内皮細胞 / RNA干渉 / ノックアウトマウス / フォルスコリン

Research Abstract

Multidrug resistance protein 4(MRP4) is a membrane protein that belongs to ABC transporter superfamily. In vitro analysis using human retinal microvascular endothelial cells(HRECs) showed that MRP4 knockdown enhanced cell migration, suppressed apoptosis. Moreover, MRP4 knockdown HRECs assembled and aggregated into a massive tube-like structure in a Matrigel-based tube formation assay. Functional analysis using Mrp4 knockout mice demonstrated abnormal increase in capillary density in developing retina after intraperitoneal injections of forskolin which increase the intracellular level of cAMP, an important substrate for Mrp4. These results suggest that MRP4 has anti-angiogenic properties in retinal angiogenesis.

Research Products

• [Journal Article] MRP4 knockdown enhances migration, suppresses apoptosis, and produces aggregated morphology in human retinal vascular endothelial cells (2010)
  • Author(s): Tagami M, Kusuhara S, Imai H, Uemura A, Honda S, Tsukahara Y, Negi A
  • Journal Title: Biochem Biophys Res Commun Volume: Vol.400 Pages: 593-598
• [Journal Article] MRP4 knockdown enhances migration, suppresses apoptosis, and produces aggregated morphology in human retinal vascular endothelial cells. (2010)
  • Author(s): Tagami M, Kusuhara S, Imai H, Uemura A, Honda S, Tsukahara Y, Negi A
  • Journal Title: Biochem Biophys Res Commun. Volume: Vol.400 Pages: 593-598
  • Peer Reviewed
• [Presentation] ABCトランスポーターと網膜血管新生 (2011)
  • Author(s): 田上瑞記、楠原仙太郎、今井尚徳、根木昭
  • Organizer: 第15回眼科分子生物学研究会
  • Place of Presentation: 宮崎県ワールドコンベンションセンター
  • Year and Date: 2011-01-22
• [Presentation] ABCトランスポーターと網膜血管新生 (2011)
  • Author(s): 田上瑞記、楠原仙太郎、今井尚徳、根木昭
  • Organizer: 第15回眼科分子生物学研究会
  • Place of Presentation: 宮崎県ワールドコンベンションセンター(宮崎県)
  • Year and Date: 2011-01-22
• [Presentation] Knockdown of Multidrug Resitance-Associated Protein 4 by siRNA Enhances Cell Migration and Tube Formation in Human Retinal Endothelial Cells (2010)
  • Author(s): Mizuki Tagami, Sentaro Kusuhara, Hisanori Imai, Shigeru Honda, Yasutomo Tsukahara, Akira Negi
  • Organizer: ARVO 2010 annual meeting
  • Place of Presentation: Fort Lauderdale、米国
  • Year and Date: 2010-05-02
• [Presentation] Knockdown of Multidrug Resitance-Associated Protein 4 by siRNA Enhances Cell Migration and Tube Formation in Human Retinal Endothelial Cells. (2010)
  • Author(s): Mizuki Tagami, Sentaro Kusuhara, Hisanori Imai, Shigeru Honda, Yasutomo Tsukahara, Akira Negi
  • Organizer: ARVO 2010 annual meeting
  • Place of Presentation: Fort Lauderdale, (米国)
  • Year and Date: 2010-05-02