Cloning and characterization of SDF-1γ a novel SDF-1 chemokine transcript with developmentally regulated expression in the nervous system

Cloning and characterization of SDF-1γ a novel SDF-1 chemokine transcript with developmentally regulated expression in the nervous system
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DOI:
10.1046/j.1460-9568.2000.00048.x
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发表时间:
2000-06-01
影响因子:
3.4
通讯作者:
Müller, HW
Müller, HW
中科院分区:
医学3区
文献类型:
--
作者:
Gleichmann, M;Gillen, C;Müller, HW

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细胞因子SDF-1 α和SDF-1 β是CXC(α)趋化因子的两种选择性剪接变体,在物种间高度保守。SDF-1 α被证明是一种B细胞成熟因子,是CXCR 4(LESTR/融合蛋白)趋化因子受体的配体,从而抑制嗜T细胞HIV-1毒株的复制并诱导人类神经元细胞系中的细胞死亡。在这份报告中,大鼠SDF-1 β cDNA的克隆和一个新的SDF-1亚型,SDF-1 γ,提出。使用北方印迹分析,在不同组织中研究了两种亚型的表达模式,结果表明,在中枢和外周神经系统的出生后发育期间,SDF-1 β-和SDF-1 γ-mRNA的表达是反向调节的。虽然SDF-1 β-mRNA是胚胎和出生后早期神经组织中的主要亚型,但SDF-1 γ-mRNA在成年期以较高水平表达。周围神经损伤后,观察到SDF-1 β-mRNA表达的短暂增加。如原位杂交所示,神经元和雪旺细胞是神经系统中SDF-1 β和SDF-1 γ mRNA的主要细胞来源。计算机辅助分析显示,这两个转录本编码分泌肽与推定的蛋白水解切割位点,可能会产生新的神经肽。
The cytokines SDF-1 alpha and -1 beta are two alternatively spliced variants of the CXC (alpha) chemokines that are highly conserved among species. SDF-1 alpha was shown to function as a B-cell maturation factor, a ligand for the CXCR4 (LESTR/fusin) chemokine receptor, thereby inhibiting replication of T cell-tropic HIV-1 strains and inducing cell death in human neuronal cell lines. In this report the cloning of the rat SDF-1 beta cDNA and a new SDF-1 isoform, SDF-1 gamma, are presented. Using Northern blot analysis, the expression pattern of both isoforms was studied in different tissues and it is shown that during postnatal development of the central and peripheral nervous system SDF-1 beta- and SDF-1 gamma-mRNA expression is inversely regulated. Whilst SDF-1 beta-mRNA is the predominant isoform in embryonic and early postnatal nerve tissue, SDF-1 gamma-mRNA is expressed at higher levels in adulthood. After peripheral nerve lesion a transient increase in SDF-1 beta-mRNA expression is observed. As revealed by in situ hybridization, neurons and Schwann cells are the main cellular sources of both SDF-1 beta and SDF-1 gamma mRNAs in the nervous system. Computer-assisted analysis revealed that both transcripts encode secreted peptides with putative proteolytic cleavage sites which might generate novel neuropeptides.