miR-134 was previously documented to be highly expressed in the serum from patients with acute ischemic stroke. Besides, it was demonstrated that miR-200/PHD2/HIF-1α played a part in ischemic preconditioning. For instance, miR-107 expression was elucidated to be regulated by HIF-1α under hypoxic stress conditions, such as stroke and ischemic heart disease. Besides, previous investigations demonstrated that some of the miRNAs expression was associated with tissues oxygen levels and could be stimulated by hypoxia through regulating the expression of HIF-1. Several researches have indicated that miRNAs played crucial roles in cerebral ischemia. MicroRNAs (miRNAs) are a group of non-coding RNAs, which are responsible for the regulation of post-translational mRNA expression. However, factors regulating HIF-1α expression under OGD/R-induced injury remain to be further elucidated. More importantly, oxygen-glucose deprivation (OGD)-induced cerebral injury is a frequently used model in the research on ischemic stroke in vitro. Another study disclosed that suppression of HIF-1α effectively alleviated ischemia/reperfusion-induced brain injury. Bok’s results showed that HIF-1α could increase the survival rate of neurons after ischemic stroke. For instance, Shi reported the neuroprotective role of HIF-1α in cerebral ischemia.
Growing studies have reported that HIF-1α played a vital role in cerebral ischemia. Therefore, HIF-1α is stabilized in the cytoplasm and can be transported to the nucleus to regulate the expression of its target genes. However, under hypoxic condition, HIF-1α can’t be hydroxylated due to short of oxygen inactivating proline hydroxylase activity. In normoxia condition, HIF-1α expression is extremely low. HIF-1α is also a pivotal regulator of hypoxia, which can regulate over 80 downstream genes to acclimatize cells to low oxygen condition. Hypoxia-inducible factor-1 alpha (HIF-1α), a transcription factor, can regulate the expression of various genes that participating in the processes of angiogenesis, cellular survival and metabolism. Therefore, finding effective therapies for cerebral stroke is urgently required. Whereas, we have few effective therapies to improve the situation due to the poor understanding of the underlying mechanism of stroke-induced cell death. Numerous surviving stroke victims spend the rest of their lives in disability. Cerebral stroke, which has the characteristics of high incidence, morbidity and disability, often results in brain tissue damage. The incidence of ischemic stroke accounts for 60%–70% of the total cerebral stroke. Cerebral stroke includes hemorrhagic stroke and ischemic stroke, which is induced by vascular obstruction or blood vessels burst. Cerebral stroke is one of the acute cerebrovascular diseases. Stroke is a major cause of disability and early adult death around the world.
Our present study reported that HIF-1α overexpression protected PC12 cells against OGD/R-evoked injury via down-regulation of miR-134, which making HIF-1α and miR-134 to be promising targets for cerebral stroke therapy. Up-regulation of miR-134 notably counteracted HIF-1α overexpression-triggered neuro-protective impacts on OGD/R-evoked injury and ERK1/2 and JAK1/STAT3 pathways. Besides, miR-134 was also down-regulated by HIF-1α overexpression in PC12 cells. HIF-1α overexpression attenuated OGD/R-evoked injury in PC12 cells and remarkably reversed OGD/R-triggered inhibitory effects on ERK1/2 and JAK1/STAT3 pathways. HIF-1α expression was markedly increased by OGD/R treatment.
Results showed that OGD/R treatment induced cell injury through reducing viability, while enhancing apoptosis that was validated by the elevated ratios of C/P-PARP and C/P-caspase-3. Variations of protein levels were evaluated by employing western blot. Cell transfections were conducted to overexpress HIF-1α and miR-134. CCK-8, flow cytometry and qRT-PCR were conducted to determine the variations of cell viability, apoptosis and gene expression, respectively. OGD/R treatment was conducted on PC12 cells to simulate ischemic injury. Our study explored the influences and mechanisms of HIF-1α on OGD/R-evoked injury. Nowadays, searching for new therapeutic targets for cerebral stroke treatment are still in urgent need.