Functional analysis of PDGF inducing neural stem cell differentiation.

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590381
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: University of Toyama
• Principal Investigator: ISHII Yoko University of Toyama, 大学院・医学薬学研究部(医学), 准教授 (00361949)
• Co-Investigator(Kenkyū-buntansha): SASAHARA Masakiyo 富山大学, 大学院・医学薬学研究部(医学), 教授 (20154015) ; TAKASAKI Ichiro 富山大学, 生命科学研究センター, 助教 (00397176)
• Project Period (FY): 2008 – 2010
• Keywords: 細胞 / 血小板由来増殖因子 / 神経幹細胞 / 細胞分化

Research Abstract

PDGFR-β knockout neural stem cells showed a higher rate of apoptosis and significant decrease in proliferation. They demonstrated reduced capacities of migration and neuronal differentiation in response to not only PDGF-BB but also bFGF. bFGF increased the activity of the PDGFR-β promoter as well as the expression and phosphorylation of PDGFR-β. PDGFR-β is needed for survival, and the effects of bFGF in migration and neural differentiation of the cells may be potentiated by induction of PDGFR-β. PDGFR-β knockout mice exhibited delayed recovery of body weight and behavior, as well as a larger infarction volume after middle cerebral artery occlusion (MCAO) than controls. Astroglial scar formation was less in PDGFR-β knockout mice than in controls. These data suggest that PDGFR-β signaling is crucial for endogenous tissue repair and functional recovery following cerebral ischemia by vascular maturation and glial scar formation.

Research Products

• [Journal Article] Roles of PDGF receptor-beta in the structure and function of postnatal kidney glomerulus. (2010)
  • Author(s): Nakagawa T, Izumino K, Ishii Y, Oya T, Hamashima T, Shen J, Ishizawa S, Tomoda F, Fujimori T, Nabeshima Y, Inoue H, Sasahara M.
  • Journal Title: Nephrology Dialysis Transplantation Vol.26 Pages: 458-468
  • Peer Reviewed
• [Journal Article] function by selectively competing with AIB1for binding to ER in ER-positive breast cancer cells. (2010)
  • Author(s): Dong XY, Sun X, Guo P, Li Q, Sasahara M, Ishii Y
  • Journal Title: J.Biol.Chem. Vol.112 Pages: 32801-32809
  • Peer Reviewed
• [Journal Article] Neuroprotective effects of PDGF ag ainst involved. (2010)
  • Author(s): Zheng L, Ishii Y, Tokunaga A, Hamashima T, Shen J, Zhao QL, Ishizawa S, Fujimori T, Nabeshima Y, Mori H, Kondo T, Sasahara M.
  • Journal Title: J Neurosci Res. Vol.88 Pages: 1273-1284
  • Peer Reviewed
• [Journal Article] Involvement of Platelet-Derived Growth Factor-BB and Its Receptor-beta in Hypoxia-Induced Depression of ExcitatorySynaptic Transmission in the Nucleus Tractus Solitarius of Mice. (2010)
  • Author(s): Ohi Y, Ishii Y, Sasahara M, Haji A.
  • Journal Title: J Pharmacol Sci. Vol.112 Pages: 477-481
  • Peer Reviewed
• [Journal Article] Activation of MAP kinases, Akt and PDGF receptors in injured peripheral nerves. (2009)
  • Author(s): Yamazaki T, Sabit H, Oya T, Ishii Y, Hamashima T, Tokunaga A, Ishizawa S, Jie S, Kurashige Y, Matsushima T, Furuta I, Noguchi M, Sasahara M.
  • Journal Title: J Peripher Nerv Syst. Vol.14 Pages: 165-176
  • Peer Reviewed
• [Journal Article] Hypothermia during ischemia protects against neuronal death but not acute brain edema following transient forebrain ischemia in mice. (2009)
  • Author(s): Doshi M, Kuwatori Y, Ishii Y, Sasahara M, Hirashima Y.
  • Journal Title: Biol Pharm Bull. Vol.32 Pages: 1957-1961
  • Peer Reviewed
• [Journal Article] Mohafez OMM, Sasahara M, and Hiraga K. Mutation-, aging-, and gene-dosage-dependent accumulation of FENIB-type neuroserpin (G392E) in ERs and lysosomes of neurons in transgenic mice. (2008)
  • Author(s): Takasawa A, Kato I, Takasawa K, Ishii Y, Yoshida T, Shehata MH, Kawaguchi H, Mohafez OMM, Sasahara M, Hiraga K.
  • Journal Title: Vol.283 Pages: 35606-35613
  • Peer Reviewed
• [Journal Article] A novel model of insul in-dependent diabetes with renal and retinal lesions by transgenic expression of CaMK IIalpha (Thr286Asp) in pancreatic beta-cells. (2008)
  • Author(s): Kato I, Oya T, Suzuki H, Takasawa K, Ich san AM, Nakada S.Ishii Y, Shimada Y, Sasahara M, Tobe K, Takasawa S, OkamotoH, Hiraga K.
  • Journal Title: Diabetes Metab.Res.Rev. Vol.24 Pages: 486-497
  • Peer Reviewed
• [Journal Article] PDGF receptor is a potent regulator of mesenchymal stromal cell function. (2008)
  • Author(s): Tokunaga A, Oya T, Ishii Y, Motomura H, Nakamura C, Ishizawa S, Fujimori T, Nabeshima Y, Umezawa A, Kanamori M, Kimura T., Sasahara M.
  • Journal Title: J.Bone Miner.Res. Vol.23 Pages: 1519-1528
  • Peer Reviewed
• [Journal Article] Characterization of neuroprogenitor cells expressing the PDGF -receptor within the subventricular zone of postnatal mice. (2008)
  • Author(s): Ishii Y, Matsumoto Y, Watanabe R, Elmi M, Fujimori T, Nissen J, Cao Y, Nabeshima Y, Sasahara M, Funa K.
  • Journal Title: Mol.Cell.Neurosci. Vol.37 Pages: 507-518
  • Peer Reviewed
• [Presentation] Impaired Glomerular Adaptability Against Subtotal Nephrectomy after Conditional Knock-Out of Platelet-Derived Growth Factor Receptor (PDGFR)-β in Mice. (2010)
  • Author(s): Nakagawa N, Ichikawa K, Yamazaki H, Hamashima T, Shen J, Ishii Y, Tomoda F, Inoue H, Sasahara M
  • Organizer: The American Society of Nephrology, Renal Week 2010
  • Place of Presentation: Denver, CO.
  • Year and Date: 20101116-20101121
• [Presentation] Conditional depletion of PDGF-β receptor gene in the central nervous system induced deficits in higher brain functions in mice. (2010)
  • Author(s): Nguyen PTH, Hori E, Zhao J, Li R, Urakawa S, Uwano T, Hamashima T, Ishii Y, Matsushima T, Sasahara M, Ono T, Nishijo H.
  • Organizer: 第57回中部日本生理学会
  • Place of Presentation: 豊明
  • Year and Date: 20101015-20101016
• [Presentation] The Involvement of PDGFR-β in the Maturation of Blood Vessel after Focal Cerebral Ischemia. (2010)
  • Author(s): Shen J, Ishii Y, Xu G, Hamashima T, Matsushima T, Yamamoto S, Takatsuru Y, Nabekura J, Sasahara M
  • Organizer: The 33rd Annual Meeting of the Japan Neuroscience
  • Place of Presentation: Kobe.
  • Year and Date: 20100902-20100904
• [Presentation] Neurovascular signaling of PDGF receptor beta protects CNS from insults, a study using conditional knockout mouse. (2010)
  • Author(s): 笹原正清, 石井陽子, 申杰, 濱島丈
  • Organizer: BIT'S 1st Annual World Congress of Neuro Talk 2010
  • Place of Presentation: Singapore.
  • Year and Date: 20100625-20100628
• [Presentation] The Role for PDGFR-s as a Positive Regulator of Vessels Maturation after Focal Cerebral Ischemia in Mice. (2010)
  • Author(s): 申杰, 石井陽子, 濱島丈, 笹原正清
  • Organizer: BIT'S 1st Annual World Congress of Neuro Talk 2010
  • Place of Presentation: Singapore.
  • Year and Date: 20100625-20100628
• [Presentation] マウス局所脳虚血後の修復過程を正に制御する因子としてのPDGFR-βの役割 (2010)
  • Author(s): 申杰, 石井陽子, 徐桂華, 石澤伸, 濱島丈, 倉茂洋一, 松島貴子, 笹原正清
  • Place of Presentation: 東京
  • Year and Date: 20100427-20100429
• [Presentation] Roles of PDGFR-β in the postnatal kidney glomerulus. (2009)
  • Author(s): Nakagawa T., Izumino K, Tokunaga A, Ishii Y, Oya T, Hamashima T, Shen J, Ishizawa S, Tomoda F., Inoue H., Fujimori T., Nabeshima Y., Sasahara M
  • Organizer: ASN (American Society of Nephrology) Renal Week 2009
  • Place of Presentation: San Diego, CA.
  • Year and Date: 20091011-20091027
• [Presentation] 末梢神経の再生におけるPDGF受容体および細胞シグナル活性化の解析 (2009)
  • Author(s): 山崎隆志, 石井陽子, 濱島丈, 石澤伸, 尾矢剛志, Sabit H., 徐桂華, 松島貴子, 笹原正清
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都
  • Year and Date: 20090501-20090503
• [Presentation] Cultured neuron deficit in PDGFR-ss vulnerable to oxidative stress. (2009)
  • Author(s): 笹原正清, 鄭蓮順, 石井陽子, 濱島丈, 申杰, 徐桂華, 石澤伸
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都
  • Year and Date: 20090501-20090503
• [Presentation] Role of PDGF β-receptor signaling in the neurogenesis of postnatal mouse brain. (2008)
  • Author(s): 石井陽子, 鮒恵子, 笹原正清
  • Organizer: The 31st Annual Meeting of the Japan Neuroscience Society.
  • Place of Presentation: Tokyo.
  • Year and Date: 20080709-20080711
• [Presentation] Cultured neuron deficit in PDGF receptor is vulnerable to oxidative stress. (2008)
  • Author(s): Zheng L, Ishii Y, Hamashima T, Shen J, Ishizawa S., Sasahara M
  • Organizer: The 31st Annual Meeting of the Japan Neuroscience Society.
  • Place of Presentation: Tokyo.
  • Year and Date: 20080709-20080711
• [Presentation] PDGF Receptor β is a Potent Regulator of Mesenchymal Stromal Cell Function. (2008)
  • Author(s): 徳永綾乃, 尾矢剛志, 石井陽子, 石澤伸, 濱島丈, 藤森俊彦, 鍋島陽一, 梅澤明弘, 笹原正清
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
  • Year and Date: 20080515-20080517
• [Presentation] 神経幹細胞分化におけるPDGFR-βの役割の検討 (2008)
  • Author(s): 石井陽子, 鮒恵子, 笹原正清
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
  • Year and Date: 20080515-20080517
• [Remarks] ホームページ
  • URL: http://www.med.u-toyama.ac.jp/patho12/index.html