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大鼠脊髓挫伤损伤后神经祖细胞和神经胶质细胞中HLH Id基因家族的上调。

Upregulation of the HLH Id gene family in neural progenitors and glial cells of the rat spinal cord following contusion injury.

作者信息

Tzeng S F, Bresnahan J C, Beattie M S, de Vellis J

机构信息

Department of Neurobiology, Mental Retardation Research Center, UCLA School of Medicine, 760 Westwood Plaza, Los Angeles, CA 90024-1759, USA.

出版信息

J Neurosci Res. 2001 Dec 15;66(6):1161-72. doi: 10.1002/jnr.10089.

DOI:10.1002/jnr.10089
PMID:11746449
Abstract

Spinal cord injury (SCI) leads to a complex sequence of cellular responses, including astrocyte activation, oligodendrocyte death, and ependymal cell proliferation. Inhibitors of DNA binding (Id1, Id2, Id3) belong to a helix-loop-helix (HLH) gene family. Id genes have been implicated in playing a vital role in the proliferation of many cell types, including astrocytes and myoblasts. In the present study, the expression of Id family members in spinal cord after contusion injury was investigated by in situ hybridization. Id1, Id2, and Id3 mRNA expression was upregulated 5 mm rostral and caudal to the lesion center, and reached maximal levels 3 days after SCI. In addition, cell populations expressing Id1, Id2, and Id3 mRNA were maximally increased 3 days after SCI. The increase in Id2 and Id3 mRNA expression and Id2 and Id3 mRNA+ cells was still observed at 8 days. The Id mRNA expressing cells were phenotyped by combining immunostaining of cell-specific markers with in situ hybridization. Glial fibrillary acidic protein (GFAP)+ astrocytes were found to express all three Id mRNA, whereas S-100alpha+ astrocytes only expressed high levels of Id2 and Id3 mRNA. Cells having a neural progenitor morphology and the marker nestin appeared after SCI and they expressed Id1, Id2, and Id3 mRNA. Interestingly, some Rip+ oligodendrocytes located in the areas close to the central canal expressed Id3 mRNA after injury. In conclusion, Id genes are upregulated in a time-dependent manner in astrocytes, oligodendrocytes, and neural progenitor subpopulations after SCI, suggesting that they play major roles in cellular responses following SCI.

摘要

脊髓损伤(SCI)会引发一系列复杂的细胞反应,包括星形胶质细胞活化、少突胶质细胞死亡和室管膜细胞增殖。DNA结合抑制因子(Id1、Id2、Id3)属于螺旋-环-螺旋(HLH)基因家族。Id基因在包括星形胶质细胞和成肌细胞在内的多种细胞类型的增殖中起着至关重要的作用。在本研究中,通过原位杂交研究了挫伤性损伤后脊髓中Id家族成员的表达情况。Id1、Id2和Id3 mRNA表达在损伤中心头侧和尾侧5毫米处上调,并在脊髓损伤后3天达到最高水平。此外,脊髓损伤后3天,表达Id1、Id2和Id3 mRNA的细胞数量最多。在8天时仍可观察到Id2和Id3 mRNA表达以及Id2和Id3 mRNA+细胞的增加。通过将细胞特异性标志物的免疫染色与原位杂交相结合,对表达Id mRNA的细胞进行了表型分析。发现胶质纤维酸性蛋白(GFAP)+星形胶质细胞表达所有三种Id mRNA,而S-100α+星形胶质细胞仅高水平表达Id2和Id3 mRNA。脊髓损伤后出现具有神经祖细胞形态且标记物为巢蛋白的细胞,它们表达Id1、Id2和Id3 mRNA。有趣的是,一些位于中央管附近区域的Rip+少突胶质细胞在损伤后表达Id3 mRNA。总之,脊髓损伤后Id基因在星形胶质细胞、少突胶质细胞和神经祖细胞亚群中呈时间依赖性上调,表明它们在脊髓损伤后的细胞反应中起主要作用。

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