【摘 要】
：
Our previous study has shown that the transcription factor Krüppel-like factor 7 (KLF7) promotes peripheral nerve regeneration and motor function recovery after spinal cord injury. KLF7 also participates in traumatic brain injury, but its regulatory mecha
【机 构】
：
Institute of Neural Tissue Engineering,Mudanjiang Medical University,Mudanjiang,Heilongjiang Provinc
论文部分内容阅读
Our previous study has shown that the transcription factor Krüppel-like factor 7 (KLF7) promotes peripheral nerve regeneration and motor function recovery after spinal cord injury. KLF7 also participates in traumatic brain injury, but its regulatory mechanisms remain poorly understood. In the present study, an HT22 cell model of traumatic brain injury was established by stretch injury and oxygen- glucose deprivation. These cells were then transfected with an adeno-associated virus carrying KLF7 (AAV-KLF7). The results revealed that, after stretch injury and oxygen-glucose deprivation, KLF7 greatly reduced apoptosis, activated caspase-3 and lactate dehydrogenase, downregulated the expression of the apoptotic markers B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) and cleaved caspase-3, and increased the expression of βIII-tubulin and the antiapoptotic marker Bcl-2. Furthermore, KLF7 overexpression upregulated Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) phosphorylation in HT22 cells treated by stretch injury and oxygen- glucose deprivation. Immunoprecipitation assays revealed that KLF7 directly participated in the phosphorylation of STAT3. In addition, treatment with AG490, a selective inhibitor of JAK2/STAT3, weakened the protective effects of KLF7. A mouse controlled cortical impact model of traumatic brain injury was then established. At 30 minutes before modeling, AAV-KLF7 was injected into the ipsilateral lateral ventricle. The protein and mRNA levels of KLF7 in the hippocampus were increased at 1 day after injury and recovered to normal levels at 3 days after injury. KLF7 reduced ipsilateral hippocampal atrophy, decreased the injured cortex volume, downregulated Bax and cleaved caspase-3 expression, and increased the number of 5-bromo-2′-deoxyuridine-positive neurons and Bcl-2 protein expression. Moreover, KLF7 transfection greatly enhanced the phosphorylation of JAK2 and STAT3 in the ipsilateral hippocampus. These results suggest that KLF7 may protect hippocampal neurons after traumatic brain injury through activation of the JAK2/STAT3 signaling pathway. The study was approved by the Institutional Review Board of Mudanjiang Medical University, China (approval No. mdjyxy-2018-0012) on March 6, 2018.
其他文献
Age-related macular degeneration: Age-related macular degeneration (AMD) is a retinal degenerative disorder, characterized by the irreversible loss of the central vision during ageing. This chronic, progressive disease has been estimated to currently affe
The dentate gyrus subregion of the mammalian hippocampus is an adult neural stem cell niche and site of lifelong neurogenesis.Hypotheses regarding the role of adult-born neuron synaptic integration in hippocampal circuit function are framed by robust esti
It remains unclear whether limitations in activities of daily living (ADL) increase the risk of stroke in older Chinese adults. This longitudinal study used data from the Chinese Longitudinal Healthy Longevity Survey to investigate the effects of limitati
Reperfusion therapy is the preferred treatment for ischemic stroke, but is hindered by its short treatment window, especially in patients with diabetes whose reperfusion after prolonged ischemia is often accompanied by exacerbated hemorrhage. The mechanis
Although some short-term follow-up studies have found that individuals recovering from coronavirus disease 2019 (COVID-19) exhibit anxiety, depression, and altered brain microstructure, their long-term physical problems, neuropsychiatric sequelae, and cha
Damage to the vestibular sense organs evokes static and dynamic deficits in the eye movements, posture and vegetative functions. After a shorter or longer period of time, the vestibular function is partially or completely restored via a series of processe
It is well known that diabetic retinopathy is a neurovascular disease that is accompanied by dysfunction of neurovascular units composed of neurons, glial cells, and vascular cells (Antonetti et al., 2012; Figure 1). Many studies have reported that the ne
Neurotrophins have been recognized for decades for their beneficial effects on growth, survival, and maintenance in the central nervous system, all of which suggest potential therapeutic utility. Although understanding and harnessing the activity of neuro
Alzheimer\'s disease (AD) is a progressive neurodegenerative condition that goes from mild cognitive impairment in prodromal disease to severely disabling deficits in advanced stages. The risk for AD development, as well as progression and severity, cle
The dying-back hypothesis holds that the damage to neuromuscular junctions and distal axons in amyotrophic lateral sclerosis occurs at the earliest stage of the disease. Previous basic studies have confirmed early damage to neuromuscular junctions, but it