Effect of X-rays on transcript expression of rat brain microvascular endothelial cells: role of calcium signaling in X-ray-induced endothelium damage
Effect of X-rays on transcript expression of rat brain microvascular endothelial cells: role of calcium signaling in X-ray-induced endothelium damage
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DOI：
10.1042/bsr20193760
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发表时间：
2020-04-28
影响因子：
4
通讯作者：
Shen, Bing
中科院分区：
文献类型：
--
作者：
Wu, Qibing;Fang, Yang;Shen, Bing
放射性脑水肿是放射治疗的一种严重不良反应。虽然引起放射性脑水肿的原因很多，但其发病机制尚不清楚，临床治疗也不理想。因此，了解脑放疗后脑微血管内皮细胞(BMEC)转录组的差异表达可能有助于阐明放射性脑水肿的发病机制。本研究使用RNA-Seq技术鉴定了383个在对照和X射线处理的原代培养的大鼠BMEC之间差异表达的BMEC转录本(许多是2倍或更高；P<；0.05)。与对照组相比，X射线处理的BMECs有183个转录显著上调，200个显著下调。差异表达基因与细胞周期、细胞凋亡、血管通透性和细胞外连接等生物学过程有关。X射线处理的BMECs的功能变化包括钙信号、肌醇磷脂3-激酶-Akt信号和蛋氨酸降解。这些结果表明，辐射对转录产物的表达有很大的影响，这些差异表达基因所编码的蛋白质可能在放射治疗所致的脑水肿中起重要作用。我们的发现提供了对放射诱发脑水肿的分子机制的更多见解，并可能有助于开发这种放射治疗不良反应的临床治疗方法。
Radiation-induced brain edema is a serious adverse effect of radiotherapy. Although there aremany causes of radiation-induced brain edema, the pathogenesis is not clear and clinical treatment is not ideal. Therefore, knowing the differential expression of the brain microvascular endothelial cell (BMEC) transcriptome after brain radiotherapy may shed light on the pathogenesis of radiation-induced brain edema. The present study used RNA-Seq technique to identify 383 BMEC transcripts differentially expressed (many 2-fold or higher; P < 0.05) between control and X-ray-treated primary cultured rat BMECs. Compared with controls, X-ray-treated BMECs had 183 significantly up-regulated transcripts and 200 significantly down-regulated transcripts. The differentially expressed genes were associated with the biological processes of the cell cycle, apoptosis, vascular permeability, and extracellular junctions. The functional changes identified in the X-ray-treated BMECs included Ca2+ signaling, phosphoinositide 3-kinase-Akt signaling, and methionine degradation. These results indicated that transcript expression was substantially affected by radiation exposure and the proteins encoded by these differentially expressed genes may play a significant role in radiotherapy-induced brain edema. Our findings provide additional insight into the molecular mechanisms of radiation-induced brain edema and may be helpful in the development of clinical treatment of this adverse reaction to radiotherapy.