Transcriptomic Profiling Reveals the Antiapoptosis and Antioxidant Stress Effects of Fos in Ischemic Stroke.
Transcriptomic Profiling Reveals the Antiapoptosis and Antioxidant Stress Effects of Fos in Ischemic Stroke.
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转录组分析揭示 Fos 在缺血性中风中的抗细胞凋亡和抗氧化应激作用
DOI：
10.3389/fneur.2021.728984
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发表时间：
2021
影响因子：
3.4
通讯作者：
Peng J
中科院分区：
文献类型：
--
作者：
Mu Q;Zhang Y;Gu L;Gerner ST;Qiu X;Tao Q;Pang J;Dipritu G;Zhang L;Yin S;Jiang Y;Peng J
动脉高血压被认为是中风最普遍的危险因素。先前获得的病理生理学和临床数据都表明，动脉高血压的血流动力学性质与组织缺血性损伤风险的增加之间存在很强的相关性。然而，高血压和缺血性脑卒中（IS）之间的特定分子相互作用的知识是有限的。在本研究中，我们对卒中易发自发性高血压大鼠脑组织样本（GSE41452）、大脑中动脉闭塞大鼠脑组织样本（GSE97537）和IS患者外周血阵列数据（GSE22255）进行了系统的生物信息学分析。我们发现Fos是一种对动脉血压变化作出反应的即时早期基因（IEG），与IS的发生和预后有很强的相关性。为了进一步评估Fos的潜在功能，我们对HT22神经元细胞进行了氧-葡萄糖剥夺模型和RNA测序。与测序结果一致，实时定量PCR和Western blot结果显示，缺氧后3 h Fos升高，缺氧后6 h Fos恢复正常。慢病毒敲除Fos显著增加氧化应激水平、神经元凋亡，抑制线粒体功能。综上所述，Fos是高血压与IS之间的重要纽带。此外，Fos可以作为一种潜在的生物标志物，用于预防高血压患者卒中的靶向治疗，也可以作为一种潜在的靶向治疗高血压患者卒中后的细胞凋亡和氧化应激。
Arterial hypertension is considered the most prevalent risk factor for stroke. Both pathophysiologic and clinical data previously acquired suggest a strong correlation between the hemodynamic nature of arterial hypertension and an increase in the risk of ischemic insult to tissues. However, the knowledge of specific molecular interactions between hypertension and ischemic stroke (IS) is limited. In this study, we performed systematic bioinformatics analysis of stroke-prone spontaneous hypertensive brain tissue samples of rats (GSE41452), middle cerebral artery occlusion of brain tissue samples of rats (GSE97537), and peripheral blood array data of IS patients (GSE22255). We identified that Fos, an immediate-early gene (IEG) that responds to alterations in arterial blood pressure, has a strong correlation with the occurrence and prognosis of IS. To further evaluate the potential function of Fos, the oxygen–glucose deprivation model and RNA sequencing of HT22 neuronal cells were performed. Consistent with the sequencing results, real-time quantitative PCR and Western blot indicate that Fos was elevated at 3 h and returned to normal levels at 6 h after oxygen–glucose deprivation. Knock-down of Fos by lentivirus significantly increased the oxidative stress level, neuronal apoptosis, and inhibited the mitochondrial function. In conclusion, Fos acts as an important link between hypertension and IS. Furthermore, Fos can be used as a potential biomarker for target therapy in the prevention of stroke among hypertensive patients and also potential treatment targeting apoptosis and oxidative stress after its onset.
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影响因子：
15.8
作者：
Muse ED;Wineinger NE;Spencer EG;Peters M;Henderson R;Zhang Y;Barrett PM;Rivera SP;Wohlgemuth JG;Devlin JJ;Shiffman D;Topol EJ
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影响因子：
6.3
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
2.2
作者：
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通讯作者：
Charish, Jason