Transcriptomic Profiling Reveals the Antiapoptosis and Antioxidant Stress Effects of Fos in Ischemic Stroke

Abstract

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.

Exploring the hub mechanisms of ischemic stroke based on protein-protein interaction networks related to ischemic stroke and inflammatory bowel disease

“…Interestingly, the fifth cluster also mainly involves the interleukin signaling pathway, and the interaction of FOS and CCL2 genes in this cluster may play a bridging role. FOS is a potential target gene for Crohn's disease (CD) 69 , where downregulation of FOS significantly enhances oxidative stress levels, accelerates neuronal apoptosis, and inhibits mitochondrial function, increasing the risk of ischemic stroke 70 . CCL2 is intimately associated with unstable atherosclerosis as upregulated based on inflammatory stimuli.…”

Contribution of FOS in neutrophils to venous thromboembolism via miR‐144 based on bioinformatic prediction and validation

“…Mu et al confirmed that FOS has a strong correlation with the occurrence and prognosis of infantile spasm; moreover, lentivirusmediated FOS knock-down significantly increased the oxidative stress level, neuronal apoptosis and inhibited mitochondrial function (p < 0.05). 16 The AP-1/c-FOS cytokine-signalling axis can modulate recombinant TNFα leading to a strong upregulation of IL-6 mRNA expression and protein secretion, thereby promoting vascular calcification. 17 In this study, our goal was to identify novel genetic factors involved in VTE pathogenesis to facilitate its early diagnosis.…”