Human amniotic mesenchymal stem cells (hAMSCs) can be differentiated into Schwann-cell-like cells (SCLCs) in vitro. However, the underlying mechanism of cell differentiation remains unclear. In this study, we explored the phenotype and multipotency of hAMSCs, which were differentiated into SCLCs, and the expression of nerve repair-related Schwann markers, such as S100 calcium binding protein B (S-100), TNF receptor superfamily member 1B (P75), and glial fibrillary acidic protein (GFAP) were observed to be significantly increased. The secreted functional neurotrophic factors, like brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3), were determined and also increased with the differentiation time. Moreover, miR-146a-3p, which significantly decreased during the differentiation of hAMSCs into SCLCs, was selected by miRNA-sequence analysis. Further molecular mechanism studies showed that Erb-B2 receptor tyrosine kinase 2 (ERBB2) was an effective target of miR-146a-3p and that miR-146a-3p down-regulated ERBB2 expression by binding to the 3'-UTR of ERBB2. The expression of miR-146a-3p markedly decreased, while the mRNA levels of ERBB2 increased with the differentiation time. The results showed that down-regulating miR-146a-3p could promote SC lineage differentiation and suggested that miR-146a-3p negatively regulated the Schwann-like phenotype differentiation of hAMSCs by targeting ERBB2. The results will be helpful to establish a deeper understanding of the underlying mechanisms and find novel strategies for cell therapy.

中文翻译：

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miR-146a-3p通过抑制ERBB2的表达抑制hAMSCs向雪旺细胞分化

人羊膜间充质干细胞 (hAMSCs) 可以在体外分化为雪旺细胞样细胞 (SCLCs)。然而，细胞分化的潜在机制仍不清楚。在本研究中，我们探讨了分化为 SCLCs 的 hAMSCs 的表型和多能性，以及神经修复相关 Schwann 标志物的表达，如 S100 钙结合蛋白 B（S-100）、TNF 受体超家族成员 1B（P75 )，并且观察到胶质纤维酸性蛋白 (GFAP) 显着增加。分泌的功能性神经营养因子，如脑源性神经营养因子 (BDNF)、神经生长因子 (NGF) 和神经营养因子-3 (NT-3)，被测定并随着分化时间的增加而增加。此外，miR-146a-3p 在 hAMSCs 向 SCLCs 分化过程中显着降低，通过 miRNA 序列分析选择。进一步的分子机制研究表明，Erb-B2 受体酪氨酸激酶 2 (ERBB2) 是 miR-146a-3p 的有效靶标，并且 miR-146a-3p 通过与 ERBB2 的 3'-UTR 结合来下调 ERBB2 的表达。miR-146a-3p 的表达显着降低，而 ERBB2 的 mRNA 水平随着分化时间的增加而增加。结果表明下调miR-146a-3p可促进SC谱系分化，提示miR-146a-3p通过靶向ERBB2负调节hAMSCs的雪旺样表型分化。研究结果将有助于更深入地了解潜在机制并找到细胞治疗的新策略。进一步的分子机制研究表明，Erb-B2 受体酪氨酸激酶 2 (ERBB2) 是 miR-146a-3p 的有效靶标，并且 miR-146a-3p 通过与 ERBB2 的 3'-UTR 结合来下调 ERBB2 的表达。miR-146a-3p 的表达显着降低，而 ERBB2 的 mRNA 水平随着分化时间的增加而增加。结果表明下调miR-146a-3p可促进SC谱系分化，提示miR-146a-3p通过靶向ERBB2负调节hAMSCs的雪旺样表型分化。研究结果将有助于更深入地了解潜在机制并找到细胞治疗的新策略。进一步的分子机制研究表明，Erb-B2 受体酪氨酸激酶 2 (ERBB2) 是 miR-146a-3p 的有效靶标，并且 miR-146a-3p 通过与 ERBB2 的 3'-UTR 结合来下调 ERBB2 的表达。miR-146a-3p 的表达显着降低，而 ERBB2 的 mRNA 水平随着分化时间的增加而增加。结果表明下调miR-146a-3p可促进SC谱系分化，提示miR-146a-3p通过靶向ERBB2负调节hAMSCs的雪旺样表型分化。研究结果将有助于更深入地了解潜在机制并找到细胞治疗的新策略。miR-146a-3p 的表达显着降低，而 ERBB2 的 mRNA 水平随着分化时间的增加而增加。结果表明下调miR-146a-3p可促进SC谱系分化，提示miR-146a-3p通过靶向ERBB2负调节hAMSCs的雪旺样表型分化。研究结果将有助于更深入地了解潜在机制并找到细胞治疗的新策略。miR-146a-3p 的表达显着降低，而 ERBB2 的 mRNA 水平随着分化时间的增加而增加。结果表明下调miR-146a-3p可促进SC谱系分化，提示miR-146a-3p通过靶向ERBB2负调节hAMSCs的雪旺样表型分化。研究结果将有助于更深入地了解潜在机制并找到细胞治疗的新策略。