Expression of Functional γ-Aminobutyric Acid Type A Receptors in Schwann-Like Adult Stem Cells
Expression of Functional γ-Aminobutyric Acid Type A Receptors in Schwann-Like Adult Stem Cells
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DOI：
10.1007/s12031-011-9698-9
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发表时间：
2012-07-01
影响因子：
3.1
通讯作者：
Magnaghi, Valerio
中科院分区：
文献类型：
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作者：
Faroni, Alessandro;Terenghi, Giorgio;Magnaghi, Valerio
γ-氨基丁酸(GABA)受体存在于外周和中央神经胶质细胞中，调节神经胶质细胞的重要生理参数。雪旺细胞(Schwann cell，SC)是周围神经系统的神经胶质细胞，在神经再生中起重要作用，但不适合用于神经修复的生物工程。骨髓来源的成体干细胞(BM-MSC)或脂肪组织来源的成体干细胞(ASC)可以分化为SC样表型，作为SC的替代物，受到越来越多的关注。干细胞样成人干细胞表达GABA-B受体，可以调节它们的增殖。本研究的目的是研究GABA-A受体在分化干细胞中的功能表达。BM-MSC和ASC表达GABA-Aα2和β3，但不表达β1。Western印迹研究表明，干细胞样分化后，GABA-Aα2和β3受体的蛋白表达水平上调。刺激GABA-A受体后，SC、分化的BM-MSC和分化的ASC的增殖率增加。综上所述，GABA-Aα2和β3受体亚基存在于BM-MSC和ASC中，并在胶质细胞分化后上调。分化干细胞和干细胞中的GABA-A亚单位组装在调节细胞增殖的功能性受体中。功能性GABA-A和GABA-B受体是调控干细胞样细胞生理的一个可能的药理靶点。
Gamma-Aminobutyric acid (GABA) receptors are present in peripheral and central glia and modulate important physiological parameters of glial cells. Schwann cells (SC), the peripheral nervous system glial cells, play essential roles in nerve regeneration, but they are unsuitable for bioengineering of nerve repair. Increasing interest has been focused on adult stem cells derived from bone marrow (BM-MSC) or adipose tissue (ASC), which can be differentiated into SC-like phenotype and used as SC replacements. SC-like adult stem cells express GABA-B receptors that can modulate their proliferation. The aim of this study was to investigate GABA-A receptors functional expression in differentiated stem cells. BM-MSC and ASC were found to express GABA-A alpha 2 and beta 3, but not beta 1 mRNA transcripts. Protein expression levels of GABA-A alpha 2 and beta 3 receptors were upregulated following SC-like differentiation as shown by Western blot studies. GABA-A receptor stimulation with muscimol increased the proliferation rate of SC, differentiated BM-MSC and differentiated ASC. In conclusion, GABA-A alpha 2 and beta 3 receptor subunits are present in BM-MSC and ASC and upregulated following glial differentiation. GABA-A subunits in differentiated stem cells and SC assemble in functional receptors modulating cell proliferation. Functional GABA-A and GABA-B receptors represent a possible pharmacological target to modulate SC-like stem cells physiology.