miR-146a-3p suppressed the differentiation of hAMSCs into Schwann cells via inhibiting the expression of ERBB2

Abstract

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.