Analytical study on the role of platelet-derived growth factor in developing and ischemic brain.

血小板衍生生长因子在发育和缺血性脑中作用的分析研究。

• 批准号: 10670200
• 负责人: SASAHARA Masakiyo
• 金额: $ 2.43万
• 依托单位: Toyama Medical and Pharmaceutical University (1999)Shiga University of Medical Science (1998)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670200/
• 关键词: Platelet-derived growth factor; Heparin-binding epidermal growth factor; ischemia; development; brain; kidney; regeneration; neurotrophic factor; PDGF; HB-EGF; 神経; 分化; 増殖

Current project was conducted to know the role of platelet-derived growth factor (PDGF) B-chain in either developing brain or brain subjected to injury.(1) We identified two PDGF-B mRNAs (3.5 and 2.6 kb) expressed in normal rat brain. It was found that the mRNA of 2.6 kb was a truncated form of that of 3.5 kb, and that truncated form of the gene is crucial for PDGF-B translation in the neuron during development or at a acute phase of ischemia of the brain.(2) In hypoxic / ischemic encephalopathy of neonatal rat brain, PDGF-B and β-receptor expression was induced in the neurons surrounding infarction. This fact revealed PDGF-B/β-receptor system plays a role in the survival of neurons in neonatal rat brain.(3) Regenerating renal tubular epithelial cells expressed both PDGF-B and β-receptor after ischemia/reperfusion insult. Inhibitors of PDGF-B, trapidil and Ki6896, prohibited recovery of renal function and suppressed epithelial regeneration. PDGF-B is important for the regeneration of renal tubular epithelial cells after acute injury.(4) Neuronal expression of PDGF-B disappeared prior to apoptotic neuronal death selectively in CA 1 lesion of hippocampus after transient forebrain ischemia, and in retinal ganglion cells after transection of optic nerve. PDGF-B is important for the survival of neurons.(5) Currently, we are testing the function of PDGF-B in neonatal rat brain by introducing anti-sense oligonucleotide, and are getting results to show the importance of PDGF-B in the normal maturation of the brain (unpublished data).(6) We have found that Heparin-binding epidermal growth factor is widely expressed in the brain, and is upregulated in neonate and in the brain after ischemia. Function as a ligand for EGF receptor is suspected in the brain.(7) We reported mutation in the microtubule-associated protein tau in a patient of pallido-nigra-luysian degeneration.(8) We detected mossy fiber sprout in the hippocampus of rat with hereditary epilepsy.

为了解血小板衍生生长因子(PDGF)B链在脑发育和脑损伤中的作用。(1)我们鉴定了正常大鼠脑内表达的两个PDGF-B mRNAs(3.5 kb和2.6kb)。发现2.6kb的基因是3.5kb的截短型基因，该基因的截短型在发育期间或脑缺血急性期的神经元中对PDGF-B的翻译起关键作用。(2)在新生大鼠缺氧/缺血性脑病中，脑梗塞周围的神经元诱导了PDGF-B和β-受体的表达。提示PDGF-B/β-受体系统在新生大鼠脑内神经元存活中起重要作用。(3)再生肾小管上皮细胞在缺血/再灌注损伤后同时表达PDGF-B和β-受体。PDGF-B的抑制剂曲匹地尔和Ki6896抑制肾功能的恢复和抑制上皮细胞的再生。PDGF-B在急性肾小管上皮细胞损伤后的再生中起重要作用。(4)在短暂性前脑缺血后的CA1区和视神经切断后的视网膜神经节细胞中，PDGF-B的神经元表达在凋亡神经元死亡前选择性消失。PDGF-B对于神经元的存活至关重要。(5)目前，我们正在通过引入反义寡核苷酸来检测PDGF-B在新生大鼠大脑中的功能，并正在获得结果，表明PDGF-B在大脑的正常成熟中的重要性(未发表的数据)。(6)我们发现肝素结合的表皮生长因子在大脑中广泛表达，并在新生大鼠和缺血后的脑组织中上调。(7)我们报道了一例苍白球-黑质-鲁伊斯变性患者微管相关蛋白tau的突变。(8)我们在遗传性癫痫大鼠的海马区检测到苔藓纤维发芽。

项目成果

Nakagawa T, Sasahara M, Hayase Y, Haneda M, Yasuda H, Kikkawa R, Higashiyama S, Hazama F: "Neuronal and glial expression of heparin-binding EGF-like growth factor in central nervous system of prenatal and early-postnatal rat."Brain Res Dev Brain Res. 108(

Nakakawa T、Sasahara M、Hayase Y、Haneda M、Yasuda H、Kikkawa R、Higashiyama S、Hazama F：“产前和产后早期大鼠中枢神经系统中肝素结合 EGF 样生长因子的神经元和神经胶质表达。

Sasahara M: "Normal developing rat brain expresses a platelet-derived growth factor B chain (c-sis) mRNA truncated at the 5' end"Oncogene. 16(12). 1571-1578 (1998)

Sasahara M：“正常发育的大鼠大脑表达在 5 端截短的血小板衍生生长因子 B 链 (c-sis) mRNA”癌基因。

Nakagawa T: "Neuronal and glial expression of heparin-binding EGF-like growth factor in central nervous system of prenatal and early-postnatal rat"Brain Res Dev Brain Res. 108(1-2). 263-272 (1998)

Nakakawa T：“产前和产后早期大鼠中枢神经系统中肝素结合 EGF 样生长因子的神经元和神经胶质表达”Brain Res Dev Brain Res。

Mekada A: "Platelet-derived growth factor B-chain expression in the rat retina and optic nerve : distribution and changes after transection of the optic nerve"Vision Res. 38. 3031-3039 (1998)

Mekada A：“大鼠视网膜和视神经中血小板源性生长因子 B 链的表达：视神经横断后的分布和变化”Vision Res。

Yasuda M: "Schellenberg GD, Tanaka C. A mutation in the microtubule-associated protein tau in pallido-nigro-luysian degeneration"Neurology. 53(4). 864-868 (1999)

Yasuda M：“Schellenberg GD，Tanaka C. 苍白-黑-路易斯变性中微管相关蛋白 tau 的突变”神经病学。