Upregulation of seladin-1 and nestin expression in bone marrow mesenchymal stem cell transplantation via the ERK1/2 and PI3K/Akt signaling pathways in an Alzheimer's disease model

阿尔茨海默病模型中骨髓间充质干细胞移植中通过 ERK1/2 和 PI3K/Akt 信号通路上调 seladin-1 和 nestin 表达

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作者:Shi Yu, Yue Hei, Weiping Liu

Abstract

The aim of the present study was to determine the roles of bone marrow mesenchymal stem cell (BM-MSC) transplantation in a model of Alzheimer's disease (AD) and determine the underlying mechanism. The expression of selective Alzheimer's disease indicator-1 (Seladin-1) and nestin was detected using reverse transcription-quantitative polymerase chain reaction and western blot analysis. The phosphoinositide 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK)1/2 inhibitors, LY294002 and PD98059, were employed to evaluate the molecular mechanism. The results indicated that the mRNA and protein expression of Seladin-1 and nestin was lower in the AD group when compared with the control group. BM-MSC transplantation reversed this decrease in expression, potentially by increasing the protein expression of phosphorylated (p)-protein kinase B (Akt) and p-ERK1/2. In addition, LY294002 (the PI3K inhibitor) and/or PD98059 (the ERK1/2 inhibitor) blocked the enhancement of BM-MSC transplantation on the expression of Seladin-1 and nestin in the hippocampus. These results indicated that BM-MSC transplantation enhanced Seladin-1 and nestin expression potentially via a mechanism associated with the activation of the PI3K/Akt and ERK1/2 signaling pathways. The present study offers preliminary evidence that treatment with BM-MSCs may represent a potential therapeutic approach against brain lesions in AD.

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