奶油
马拉特1
血脑屏障
神经保护
脑缺血
医学
药理学
转录因子
基因沉默
缺血
癌症研究
内科学
化学
下调和上调
生物化学
中枢神经系统
长非编码RNA
基因
作者
Wenchen Ruan,Jingwei Li,Yang Xu,Yunjie Wang,Feng Zhao,Xu Yang,Hu‐Lin Jiang,Luyong Zhang,Juan M. Saavedra,Lei Shi,Tao Pang
标识
DOI:10.1007/s10571-018-00646-4
摘要
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA contributing to protect the blood-brain barrier (BBB) after stroke. We searched for small molecules that may up-regulate MALAT1 and focused on polydatin (PD), a natural product, as a possible candidate. PD enhanced MALAT1 gene expression in rat brain microvascular endothelial cells, reducing cell toxicity and apoptosis after oxygen and glucose deprivation (OGD). These effects correlated with reduction of inflammatory factors and enhancement of expression of BBB markers. We found opposite changes after MALAT1 silencing. We determined that C/EBPβ is a key transcription factor for PD-mediated MALAT1 expression. PPARγ activity is involved in MALAT1 protective effects through its coactivator PGC-1α and the transcription factor CREB. This suggests that PD activates the MALAT1/CREB/PGC-1α/PPARγ signaling pathway to protect endothelial cells against ischemia. PD administration to rats subjected to brain ischemia by transient middle cerebral artery occlusion (tMCAO) reduced cerebral infarct volume and brain inflammation, protected cerebrovascular endothelial cells and BBB integrity. These effects correlated with increased expression of MALAT1, C/EBPβ, and PGC-1α. Our results strongly suggest that the beneficial effects of PD involve the C/EBPβ/MALAT1/CREB/PGC-1α/PPARγ pathway, which may provide a novel therapeutic strategy for brain ischemic stroke.
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