Proliferation of human Schwann cells induced by neu differentiation factor isoforms
Proliferation of human Schwann cells induced by neu differentiation factor isoforms
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DOI：
10.1159/000017351
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发表时间：
1998-11-01
影响因子：
2.9
通讯作者：
Kim, SU
中科院分区：
文献类型：
--
作者：
Baek, SY;Kim, SU
神经分化因子（NDF）是一种44 kD多肽，是神经调节蛋白家族的成员，该家族还包括神经胶质生长因子、调蛋白和乙酰胆碱受体诱导活性。以往的研究表明，NDF/胶质生长因子/heregulin/乙酰胆碱受体活性是神经元的产物，并介导实验动物雪旺细胞的增殖、分化和基因表达。在本研究中，不同亚型的NDF在刺激人雪旺细胞增殖的功效进行了研究，在雪旺细胞富集的文化来自胎儿人背根神经节（15-20周妊娠）。检测的NDF亚型包括α 1、α 2、EGF样结构域α 2（EGF α 2）、α 3、β 1、EGF β 1、EGF β、β 2和β 3。为了评估雪旺细胞增殖，使用S-100蛋白和溴脱氧尿苷特异性抗体进行双重免疫染色。虽然用NDF α同种型（α 1、α 2、α 3和EGF α 2）处理雪旺细胞对雪旺细胞增殖几乎没有影响，但NDF β同种型（β 1、β 2、β 3、EGF β 1和EGF β）诱导雪旺细胞中大大增强的增殖。未受刺激的雪旺细胞的增殖指数为1.3 +/-0.9%，而用NDF β亚型处理的雪旺细胞的增殖指数为21.8 +/-2.2%。发现截短的β同种型如EGF β 1和EGF β保持与全长β同种型一样有效的促有丝分裂活性，表明EGF样结构域的C-末端部分负责其受体结合和随后的生物活性。
Neu differentiation factor (NDF), a 44-kD polypeptide, is a member of the neuregulin family which also includes glial growth factor, heregulin and acetylcholine-receptor-inducing activity. Previous studies have demonstrated that NDF/glial growth factor/heregulin/acetylcholine-receptor-including activity are products of neurons and mediate proliferation, differentiation and gene expression in Schwann cells of experimental animals. In the present study, the efficacy of different isoforms of NDF in stimulating human Schwann cell proliferation is investigated in Schwann-cell-enriched cultures derived from fetal human dorsal root ganglia (15-20 weeks gestation). NDF isoforms examined include alpha 1, alpha 2, EGF-like domain alpha 2 (EGF alpha 2), alpha 3, beta 1, EGF beta 1, EGF beta, beta 2 and beta 3. For the assessment of Schwann cell proliferation, double immunostaining using antibodies specific for S-100 protein and bromodeoxyuridine was used. While treatment of Schwann cells with NDF alpha isoforms (alpha 1, alpha 2, alpha 3 and EGF alpha 2) had little effect on Schwann cell proliferation, NDF beta isoforms (beta 1, beta 2, beta 3, EGF beta 1 and EGF beta) induced a greatly enhanced proliferation in Schwann cells. The proliferation index in unstimulated Schwann cells was 1.3 +/- 0.9%, whereas in Schwann cells treated with NDF beta isoforms the proliferation index was 21.8 +/- 2.2%. The finding that the truncated beta isoforms such as EGF beta 1 and EGF beta retain a mitogenic activity as potent as full-length beta isoform indicates that the C-terminal portion of the EGF-like domain is responsible for its receptor binding and subsequent biological activity.