Expression of latent transforming growth factor beta binding proteins in the rat brain

Expression of latent transforming growth factor beta binding proteins in the rat brain
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DOI:
10.1002/cne.21621
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发表时间:
2008-03-20
影响因子:
2.5
通讯作者:
Palkovits, Miklos
Palkovits, Miklos
中科院分区:
医学3区
文献类型:
--
作者:
Dobolyi, Arpad;Palkovits, Miklos

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转化生长因子β在脑中表达,具有神经保护功能,并且可能参与神经退行性疾病的发病机制。它们的细胞内加工、分泌和细胞外活化需要潜在的转化生长因子-β结合蛋白(LTBP),如外周器官中所示。在这里,我们首先报告的四种类型的LTBPs在大鼠脑中表达的基础上,逆转录聚合酶链反应(RT-PCR)和亚型有不同的地形分布的基础上,原位杂交组织化学。LTBP-1在脉络丛、大脑皮质、内侧杏仁核、丘脑前内侧核和中线核、内侧视前区、下丘脑弓状核和背内侧核、上级橄榄核和最后区等脑区有高表达水平。LTBP-3和-4是分布最广的LTBP。两者都在大脑皮层、小脑、下丘脑、杏仁核、脑干运动核团和最后区丰富。此外,在脉络丛、苍白球、丘脑前核和网状核、乳头体、黑质、红核、脑桥核、脑干感觉核团和网状结构中也有大量表达,而在海马和臂旁核中表达较多。相反,LTBP-2的表达仅限于大脑皮层、海马CA 1区神经元和穹窿周围/外侧下丘脑区域。通过双原位杂交组织化学鉴定下丘脑细胞为食欲素合成神经元,表明LTBP表达可以非常特异性地调节。我们的数据表明,每种类型的LTBPs具有高度不同的分布模式,表明LTBPs的表达在大脑中受到特异性调节。
Transforming growth factor-betas are expressed in the brain, have neuroprotective functions, and may be involved in the pathogenesis of neurodegenerative disorders. Their intracellular processing, secretion, and extracellular activation requires latent transforming growth factor-beta binding proteins (LTBPs) as demonstrated in peripheral organs. Here, we first report that the four types of LTBPs are expressed in the rat brain based on reverse-transcriptase polymerase chain reaction (RT-PCR) and that the subtypes have different topographical distributions based on in situ hybridization histochemistry. LTBP-1 has a high expression level in several brain regions including choroid plexus, cerebral cortex, medial amygdaloid nucleus, anteromedial and midline thalamic nuclei, medial preoptic area, arcuate and dorsomedial hypothalamic nuclei, superior olive, and area postrema. LTBP-3 and -4 are the most widely distributed LTBPs. Both are abundant in the cerebral cortex, cerebellum, hypothalamus, amygdala, brainstem motor nuclei, and area postrema. In addition, LTBP-3 mRNA is also abundant in the choroid plexus, globus pallidus, anterior and reticular thalamic nuclei, mamillary body, substantia nigra, red nucleus, pontine nuclei, some brainstem sensory nuclei, and reticular formation, whileLTBP-4 is more abundant in the hippocampus and the parabrachial nuclei. In contrast, the expression of LTBP-2 is restricted to cerebral cortex, CA1 neurons of the hippocampus, and perifornical/lateral hypothalamic areas. The hypothalamic cells were identified by double in situ hybridization histochemistry as orexin-synthesizing neurons, demonstrating that LTBP expression can be very specifically regulated. Our data demonstrate that each type of LTBPs have highly distinct distributional patterns suggesting that the expression of LTBPs are specifically regulated in the brain.