MAJOR CHANGES IN THE EXPRESSION OF THE MESSENGER-RNAS FOR CHOLINERGIC DIFFERENTIATION FACTOR LEUKEMIA INHIBITORY FACTOR AND ITS RECEPTOR AFTER INJURY TO ADULT PERIPHERAL-NERVES AND GANGLIA

MAJOR CHANGES IN THE EXPRESSION OF THE MESSENGER-RNAS FOR CHOLINERGIC DIFFERENTIATION FACTOR LEUKEMIA INHIBITORY FACTOR AND ITS RECEPTOR AFTER INJURY TO ADULT PERIPHERAL-NERVES AND GANGLIA
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DOI:
10.1073/pnas.91.15.7109
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发表时间:
1994-07-19
影响因子:
11.1
通讯作者:
PATTERSON, PH
PATTERSON, PH
中科院分区:
综合性期刊1区
文献类型:
--
作者:
BANNER, LR;PATTERSON, PH

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神经生成细胞因子胆碱能分化因子/白血病抑制因子(CDF/LIF)作为营养因子,增强神经元存活,并且作为分化因子,改变神经元基因表达。还有证据表明,它在成年神经组织对损伤的反应中起作用。我们通过分析CDF/LIF及其两个受体亚基在培养和体内对周围神经损伤的反应中mRNA水平的变化,进一步研究了这种可能性。使用定量RNase保护试验,我们发现CDF/LIF mRNA显着增加(176倍),在成人,但不是新生儿,交感神经节和成人背根神经节和坐骨神经器官培养24 hr. This mRNA是明确的原位杂交检测仅在这些结构的非神经元细胞。当坐骨神经在体内被切断时,CDF/LIF mRNA在紧邻病变部位的近端和远端区域中显著增加。CDF/LIF受体复合物的配体结合亚基的mRNA在培养和神经切片时有所减少。神经损伤后CDP/LIF mRNA的急剧上升进一步证明了这种细胞因子参与了对损伤的反应,这种功能与其在几种非神经组织中的创伤或感染中的假定作用重叠。
The neuropoietic cytokine cholinergic differentiation factor/leukemia inhibitory factor (CDF/LIF) acts as a trophic factor, enhancing neuronal survival, and as a differentiation factor, altering neuronal gene expression. There is also evidence that it plays a role in the response of adult neural tissue to injury. We have examined this possibility further in rats by analyzing changes in the levels of mRNAs for CDF/LIF and its two receptor subunits in response to peripheral nerve damage in culture and in vivo. Using a quantitative RNase protection assay, we find that CDF/LIF mRNA increases dramatically (176-fold) in adult, but not neonatal, sympathetic ganglia and in adult dorsal root ganglia and sciatic nerve after organ culture for 24 hr. This mRNA is clearly detectable by in situ hybridization only in the nonneuronal cells of these structures. When the sciatic nerve is transected in vivo, CDF/LIF mRNA increases significantly in the regions immediately proximal and distal to the lesion site. The mRNA for the ligand binding subunit of the CDF/LIF receptor complex decreases somewhat upon culture and nerve section. The dramatic rise in CDP/LIF mRNA after nerve injury is further evidence that this cytokine is involved in the response to damage, a function that overlaps with its postulated role in wounding or infection in several nonneural tissues.