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

本项目旨在了解血小板衍生生长因子（PDGF） b链在发育中的脑和损伤脑中的作用。(1)我们在正常大鼠脑中鉴定了两个PDGF-B mrna（3.5和2.6 kb）的表达。结果发现，2.6 kb的mRNA是3.5 kb的mRNA的截断形式，该基因的截断形式对发育期间或脑缺血急性期神经元中PDGF-B的翻译至关重要。(2)在新生大鼠脑缺氧/缺血性脑病中，PDGF-B和β-受体在梗死周围神经元中表达被诱导。这一事实揭示了PDGF-B/β受体系统在新生大鼠脑神经元存活中起着重要作用。(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抑制剂、trapidil和Ki6896抑制肾功能恢复，抑制上皮细胞再生。PDGF-B对急性损伤后肾小管上皮细胞的再生具有重要作用。(4)短暂性前脑缺血后海马CA - 1病变和视神经横断后视网膜神经节细胞中PDGF-B在凋亡性神经元死亡前选择性表达消失。PDGF-B对神经元的存活很重要。(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，并得到了PDGF-B在大脑正常成熟中的重要性的结果（未发表的数据）。(6)我们发现肝素结合表皮生长因子在大脑中广泛表达，在新生儿和缺血后的大脑中表达上调。作为EGF受体的配体在大脑中的功能被怀疑。(7)我们报道了一名苍白球-黑质-卢伊索变性患者的微管相关蛋白tau突变。(8)我们检测了遗传性癫痫大鼠海马中的苔藓纤维芽。

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oligonucleotide, and are getting results to show the importance of PDGF-B in the normal maturation of the brain (unpublished data).(6) We have found that Heparin-binding epidermal growth factor is widely expressed in the brain, and is upregulated in neonate and in the brain after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.