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

Qiancheng Mu,Long Gu,Qianke Tao,Yuxuan Zhang,Shigang Yin,Ghosh Dipritu,Stefan T Gerner,Jianhua Peng,Jinwei Pang,Lifang Zhang,Xiancheng Qiu,Yong Jiang

doi:10.3389/fneur.2021.728984

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.

Highlights

Ischemic stroke (IS) is still a leading cause of death and disability worldwide, despite a decline in stroke mortality due to improved recognition and management of cardiovascular risk factors [1, 2]
We further demonstrated that Fos exerts antiapoptosis and antioxidant stress effects in the HT22 cell oxygen–glucose deprivation (OGD) model and serves as a promising therapeutic target for the prevention and treatment of stroke
Through the gene clustering analysis of the first 5,000 of the average expression amounts of GSE41452 gene expression matrix, we found that the clusters consisted of the experimental design grouping and internal correlation, indicating that this part of the gene can represent the overall gene expression characteristics, and there were no outlier samples (Supplementary Figure 1)

Summary

Introduction

Ischemic stroke (IS) is still a leading cause of death and disability worldwide, despite a decline in stroke mortality due to improved recognition and management of cardiovascular risk factors [1, 2]. Arterial hypertension is a major robust non-modifiable risk factor for cardiovascular disease (CVD), cerebrovascular events [3]. There are no effective biomarkers for screening individuals with high stroke risk. Based on high-throughput sequencing technology, clinical and basic stroke studies have provided resource data of stroke and revealed the transcriptional regulation mechanisms and potential therapeutic targets of a series of key stroke-related genes [7]. A large number of genes and transcription factors related to hypertension have been revealed in previous studies. We questioned whether there may be some common pathophysiological processes and specific key regulator molecules between hypertension and stroke

Methods

Results

Conclusion