Siegenthaler Julie A, Miller Michael W
Department of Neuroscience and Physiology, State University of New York- Upstate Medical University, Syracuse 13210, USA.
Cereb Cortex. 2004 Jul;14(7):791-802. doi: 10.1093/cercor/bhh039. Epub 2004 Apr 14.
Transforming growth factor (TGF) beta1 regulates cell migration of non-neural cells. Hence, two hypotheses were tested: (i) that TGFbeta1 affects cell migration and the expression of associated adhesion proteins in developing cortex; and (ii) that these effects are antagonized by ethanol. The effects of TGFbeta1 (2.5-40 ng/ml) and ethanol (400 mg/dl) on cell migration were examined in organotypic cultures from fetal rat brains. Migration was determined by tracing the movement of cells pulse-labeled with bromodeoxyuridine. Cell migration was altered by TGFbeta1 in a concentration-dependent manner: at low concentrations, cell migration was promoted whereas at high concentrations TGFbeta1 impeded migration. Ethanol treatment alone reduced the rate of migration. Interestingly, the rate of cell migration in slices treated with both TGFbeta1 and ethanol was the same as that in untreated cultures. The expression of cell adhesion proteins (nCAM, integrin alpha3, alphav and beta1) was differentially effected by TGFbeta1 and/or ethanol. TGFbeta1 increased the expression of these adhesion proteins in a progressive, concentration-dependent manner. Likewise, ethanol also increased adhesion protein expression, however, combined TGFbeta1 and ethanol treatment reduced expression. Collectively, the data show that TGFbeta1 alters cell migration in the developing cortex and that the TGFbeta1 system is a target of ethanol toxicity.
转化生长因子（TGF）β1调节非神经细胞的细胞迁移。因此，我们检验了两个假设：（i）TGFβ1影响发育中皮质的细胞迁移及相关黏附蛋白的表达；（ii）乙醇可拮抗这些作用。在胎鼠脑的器官型培养物中研究了TGFβ1（2.5 - 40 ng/ml）和乙醇（400 mg/dl）对细胞迁移的影响。通过追踪用溴脱氧尿苷脉冲标记的细胞运动来确定迁移情况。TGFβ1以浓度依赖性方式改变细胞迁移：在低浓度时促进细胞迁移，而在高浓度时TGFβ1阻碍迁移。单独乙醇处理降低了迁移速率。有趣的是，同时用TGFβ1和乙醇处理的切片中的细胞迁移速率与未处理培养物中的相同。细胞黏附蛋白（神经细胞黏附分子、整合素α3、αv和β1）的表达受到TGFβ1和/或乙醇的不同影响。TGFβ1以渐进的、浓度依赖性方式增加这些黏附蛋白的表达。同样，乙醇也增加黏附蛋白表达，然而，TGFβ1和乙醇联合处理降低了表达。总体而言，数据表明TGFβ1改变发育中皮质的细胞迁移，并且TGFβ1系统是乙醇毒性的作用靶点。
