Functional analysis of PDGF inducing neural stem cell differentiation.

• 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
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• 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. (2011)
  • 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 Volume: 26 Pages: 458-468
  • Peer Reviewed
• [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] Neuroprotective effects of PDGF against oxidative stress and the signaling pathway 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: Journal of Neuroscience Research Volume: 88 Pages: 1273-1284
  • Peer Reviewed
• [Journal Article] Involvement of Platelet-Derived Growth Factor-BB and Its Receptor-beta in Hypoxia-Induced Depression of Excitatory Synaptic Transmission in the Nucleus Tractus Solitarius of Mice. (2010)
  • Author(s): Ohi Y, Ishii Y, Sasahara M, Haji A.
  • Journal Title: Journal of Pharmacological Sciences Volume: 112 Pages: 477-481
  • Peer Reviewed
• [Journal Article] ATBF1 inhibits ER function by selectively competing with AIB1 for binding to ER in ER-positive breast cancer cells. (2010)
  • Author(s): Dong XY, Sun X, Guo P, Li Q, Sasahara M, Ishii Y, Dong JT.
  • Journal Title: The Journal of Biological Chemistry Volume: 285 Pages: 32801-32809
  • Peer Reviewed
• [Journal Article] Reduced expression of the ATRX gene, a chromatin-remodeling factor, causes hippocampal dysfunction in mice. (2010)
  • Author(s): Nogami T, Beppu H, Tokoro T, Moriguchi S, Shioda N, Fukunaga K, Ohtsuka T, Ishii Y, Sasahara M, Shimada Y, Nishijo H, Li E, Kitajima I.
  • Journal Title: Hippocampus Volume: (published online)
  • Peer Reviewed
• [Journal Article] Involvement of Platelet-Derived Growth Factor-BB and Its Receptor-beta in Hypoxia-Induced Depression of Excitatory Synaptic Transmission in the Nucleus Tractus Solitarius of Mice. (2010)
  • Author(s): Ohi Y, Ishii Y, Sasahara M, Haji A.
  • Journal Title: J Pharmacol Sci. (Mar 20. [Epub ahead of print])
  • Peer Reviewed
• [Journal Article] Neuroprotective effects of PDGF against oxidative stress and the signaling pathway 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. 88 Pages: 1273-1284
  • 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
  • NAID: 130000116978
  • Peer Reviewed
• [Journal Article] Hypoxic ventilatory response in platelet-derived growth factor receptor-beta-knockout mice. (2009)
  • Author(s): Tsunekawa S, Ohi Y, Ishii Y, Sasahara M, Haji A.
  • Journal Title: J Pharmacol Sci. 110 Pages: 270-275
  • 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. 32 Pages: 1957-1961
  • NAID: 130000116978
  • 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. 14 Pages: 165-176
  • 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
• [Journal Article] Characterization of neuroprogenitor cells expressing the PDGF β-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. 37 Pages: 507-518
  • Peer Reviewed
• [Journal Article] PDGF receptor β 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. 23 Pages: 1519-1528
  • Peer Reviewed
• [Journal Article] A novel model of insulin-dependent diabetes with renal and retinal lesions by transgenic expression of CaMKIIalpha (Thr286Asp) in pancreatic beta-cells. (2008)
  • Author(s): Kato I., Oya T., Suzuki H., Takasawa K., Ichsan A. M., Nakada S., Ishii Y., Shimada Y., Sasahara M., Tobe K., Takasawa S., Okamoto H., Hiraga K.
  • Journal Title: Diabetes Metab. Res. Rev. 24 Pages: 486-497
  • Peer Reviewed
• [Journal Article] 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 M. H., Kawaguchi H., Mohafez O. M. M., Sasahara M., Hiraga K.
  • Journal Title: J. Biol. Chem. 283 Pages: 35606-35613
  • Peer Reviewed
• [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
• [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
• [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.
• [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.
• [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.
• [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.
• [Presentation] Neurovascular signaling of PDGF receptor beta protects CNS from in sults, a study using conditional knockout mouse. (2010)
  • Author(s): Sasahara M, Ishii Y, Shen J, Hamashima T.
  • Organizer: BIT'S 1st Annual World Congress of Neuro Talk 2010
  • Place of Presentation: Singapore
• [Presentation] The Role for PDGFR-s as a Positive Regulator of Vessels Maturation after Focal Cerebral Ischemia in Mice. (2010)
  • Author(s): Shen J, Ishii Y, Hamashima T, Sasahara M.
  • Organizer: BIT'S 1st Annual World Congress of Neuro Talk 2010
  • Place of Presentation: Singapore
• [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, USA
• [Presentation] Eplerenone ameliorates hepatic lipid accumulation, inflammation, and fibrosis induced by high-fat and high-fructose feeding in the liver specific SREBP1c transgenic mice. (2010)
  • Author(s): Wada T, Miyashita Y, Sasaki M, Ishii Y , Sasahara M, HTsuneki H, Sasaoka T.
  • Organizer: The 3rd international aldosterone forum in Japan
  • Place of Presentation: Tokyo, Japan
• [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 Society (Neuro 2010)
  • Place of Presentation: Kobe, Japan
• [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
• [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
• [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.
• [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
  • Organizer: ASN (American Society of Nephrology) Renal Week 2009
  • Place of Presentation: San Diego, CA
• [Presentation] Cultured neuron deficit in PDGFR-β 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
• [Presentation] マウス脳虚血中の低体温が脳浮腫および海馬神経細胞死の発生に及ぼす影響 (2009)
  • Author(s): 道志勝, 鍬取悠大, 石井陽子, 笹原正清, 平島豊
  • Organizer: 第12回日本脳低温療法学会
  • Place of Presentation: 札幌
• [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.
• [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.
• [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
• [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
• [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
• [Presentation] PDGFR-βは, 細胞内カルシウムイオン濃度上昇の抑制を介して, 酸化ストレス性細胞死から神経細胞を保護する. (2008)
  • Author(s): 鄭 蓮順, 石井陽子, 尾矢剛志, 徳永綾乃, 濱島 丈, 松島貴子, 倉茂洋一, 申 杰, 石澤 伸, 近藤 隆, 笹原正清
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
• [Presentation] Role of PDGF β-receptor signaling in the neurogenesis of postnatal mouse brain. (2008)
  • Author(s): Ishii Y., Funa K., Sasahara M.
  • Organizer: The 31st Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: Tokyo
• [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
• [Remarks] ホームページ
  • URL: http://www.med.u-toyama.ac.jp/patho12/index.html