Astragalus polysaccharide protects hypoxia-induced injury by up-regulation of miR-138 in rat neural stem cells.
Astragalus polysaccharide (APS) is the main active ingredient of astragalus and exhibits various pharmacological effects. This study aimed to investigate the effect of APS on hypoxia-induced injury in neural stem cells (NSCs). The NSCs derived from the hippocampus of rat were subjected to hypoxia incubator to establish a hypoxia model. NSCs were pretreated with APS before hypoxia injury to investigate the effect of APS. The expression of miR-138 was inhibited by transfection with miR-138 inhibitor and the miR-138 level was measured by qRT-PCR. Cell viability and apoptotic cell rates were respectively assessed by CCK-8 assay and flow cytometry assay. Western blot was performed to determine the expression of apoptosis-, JNK pathway- and p38MAPK pathway-related factors. Hypoxia exposure caused the reduction of cell viability and induction of cell apoptosis of NSCs. However, APS pretreatment attenuated the cell injury induced by hypoxia, as evidenced by increased cell viability, reduced apoptotic cells, inhibited expression of pro-apoptotic factors and enhanced expression of anti-apoptotic factor. Interestingly, higher miR-138 expression was observed in the hypoxia-injured NSCs compared with normoxia, and miR-138 expression was further up-regulated by APS pretreatment. Furthermore, miR-138 inhibitor blocked the protective effect of APS on hypoxia-injured NSCs. In addition, we found that APS inhibited the JNK and p38MAPK pathways through miR-138. In conclusion, this study demonstrated a protective effect of APS on hypoxia-induced NSC injury. The regulatory mechanism might be mediated by up-regulation of miR-138 and inhibition of the JNK and p38MAPK pathways.
['Zheng|Zebao|Z|', 'Zhao|Bing|B|']
D000818:Animals D017209:Apoptosis D027883:Astragalus Plant D015687:Cell Hypoxia D002470:Cell Survival D002478:Cells, Cultured D006624:Hippocampus D035683:MicroRNAs D058953:Neural Stem Cells D018696:Neuroprotective Agents D011134:Polysaccharides D061251:Primary Cell Culture D017207:Rats, Sprague-Dawley D015854:Up-Regulation
miR-138 Astragalus polysaccharide (APS) Neural stem cells (NSCs) Hypoxia Cell apoptosis