Krüppel-like factor 7 attenuates hippocampal neuronal injury after traumatic brain injury
| Autor: | Xiu-Mei Fu, Wen-Yuan Li, Ping Sun, Xiao-Feng Zhu, Zhen-Dong Wang, Gui-Bo Liu, Zhi-Gang Li, Duo Ma, Ying Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
oxygen-glucose deprivation Traumatic brain injury hippocampus Hippocampus apoptosis jak2/stat3 kruppel-like factor 7 neuroprotection stretch traumatic brain injury Hippocampal formation Neuroprotection Developmental Neuroscience Internal medicine medicine STAT3 RC346-429 Spinal cord injury biology business.industry JAK2/STAT3 medicine.disease Kruppel-like factor 7 Endocrinology STAT protein biology.protein Phosphorylation Neurology. Diseases of the nervous system business Research Article |
| Zdroj: | Neural Regeneration Research Neural Regeneration Research, Vol 17, Iss 3, Pp 661-672 (2022) |
| ISSN: | 1876-7958 1673-5374 2018-0012 |
| Popis: | Our previous study has shown that the transcription factor Kruppel-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. |
| Databáze: | OpenAIRE |
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