MIcroglia/macrophage-mediated erythrophagocytosis plays a crucial role in hematoma clearance after intracerebral hemorrhage.Dynamic cytoskeletal changes accompany phagocytosis.However,whether and how these changes are...MIcroglia/macrophage-mediated erythrophagocytosis plays a crucial role in hematoma clearance after intracerebral hemorrhage.Dynamic cytoskeletal changes accompany phagocytosis.However,whether and how these changes are associated with microglia/macrophage-mediated erythrophagocytosis remain unclear.In this study,we investigated the function of acetylatedα-tubulin,a stabilized microtubule form,in microglia/macrophage erythrophagocytosis after intracerebral hemorrhage both in vitro and in vivo.We first assessed the function of acetylatedα-tubulin in erythrophagocytosis using primary DiO GFP-labeled red blood cells co-cultured with the BV2 microglia or RAW264.7 macrophage cell lines.Acetylatedα-tubulin expression was significantly decreased in BV2 and RAW264.7 cells during erythrophagocytosis.Moreover,silencingα-tubulin acetyltransferase 1(ATAT1),a newly discoveredα-tubulin acetyltransferase,decreased Ac-α-tub levels and enhanced the erythrophagocytosis by BV2 and RAW264.7 cells.Consistent with these findings,in ATAT1-/-mice,we observed increased ionized calcium binding adapter molecule 1(Iba1)and Perls-positive microglia/macrophage phagocytes of red blood cells in peri-hematoma and reduced hematoma volume in mice with intracerebral hemorrhage.Additionally,knocking out ATAT1 alleviated neuronal apoptosis and pro-inflammatory cytokines and increased anti-inflammatory cytokines around the hematoma,ultimately improving neurological recovery of mice after intracerebral hemorrhage.These findings suggest that ATAT1 deficiency accelerates erythrophagocytosis by microglia/macrophages and hematoma absorption after intracerebral hemorrhage.These results provide novel insights into the mechanisms of hematoma clearance and suggest ATAT1 as a potential target for the treatment of intracerebral hemorrhage.展开更多
Background Epilepsy affects over 70 million people worldwide;however,the underlying mechanisms remain unclear.MicroRNAs(miRNAs)have essential functions in epilepsy.miRNA-9,a brain-specific/enriched miRNA,plays a role ...Background Epilepsy affects over 70 million people worldwide;however,the underlying mechanisms remain unclear.MicroRNAs(miRNAs)have essential functions in epilepsy.miRNA-9,a brain-specific/enriched miRNA,plays a role in various nervous system diseases and tumors,but whether miRNA-9 is involved in epilepsy and glioma-associated epilepsy remains unknown.Therefore,we aimed to explore the potential role of miR-9-5p in seizures and its effect on the survival of glioma patients,in order to provide new targets for the treatment of epilepsy and glioma.Methods The YM500v2 database was used to validate the expression of hsa-miR-9-5p in tissues.Moreover,qRT-PCR was performed to investigate the expression of miR-9-5p in temporal lobe epilepsy patients and rats with lithium-pilocarpine-induced seizures.Recombinant adeno-associated virus containing miR-9-5p was constructed to overexpress miR-9-5p in vivo.The effects of miR-9-5p on the behavior and electroencephalographic activities of the lithium-pilocarpine rat model of epilepsy were tested.Bioinformatics analysis was used to predict the targets of miR-9-5p and explore its potential role in epilepsy and glioma-associated epilepsy.Results The expression of miR-9-5p increased at 6 h and 7 days after lithium-pilocarpine-induced seizures in rats.Overexpression of miR-9-5p significantly shortened the latency of seizures and increased seizure intensity at 10 min and 20 min after administration of pilocarpine(P<0.05).Predicted targets of miR-9-5p were abundant and enriched in the brain,and affected various pathways related to epilepsy and tumor.Survival analysis revealed that overexpression of miR-9-5p significantly improved the survival of patients from with low-grade gliomas and glioblastomas.The involvement of miR-9-5p in the glioma-associated epileptic seizures and the improvement of glioma survival may be related to multiple pathways,including the Rho GTPases and hub genes included SH3PXD2B,ARF6,and ANK2.Conclusions miR-9-5p may play a key role in promoting epileptic seizures and improving glioma survival,probably through multiple pathways,including GTPases of the Rho family and hub genes including SH3PXD2B,ARF6 and ANK2.Understanding the roles of miR-9-5p in epilepsy and glioma and the underlying mechanisms may provide a theoretical basis for the diagnosis and treatment of patients with epilepsy and glioma.展开更多
基金supported by Science and Technology Innovation Enhancement Project of Army Medical University(to LX).
文摘MIcroglia/macrophage-mediated erythrophagocytosis plays a crucial role in hematoma clearance after intracerebral hemorrhage.Dynamic cytoskeletal changes accompany phagocytosis.However,whether and how these changes are associated with microglia/macrophage-mediated erythrophagocytosis remain unclear.In this study,we investigated the function of acetylatedα-tubulin,a stabilized microtubule form,in microglia/macrophage erythrophagocytosis after intracerebral hemorrhage both in vitro and in vivo.We first assessed the function of acetylatedα-tubulin in erythrophagocytosis using primary DiO GFP-labeled red blood cells co-cultured with the BV2 microglia or RAW264.7 macrophage cell lines.Acetylatedα-tubulin expression was significantly decreased in BV2 and RAW264.7 cells during erythrophagocytosis.Moreover,silencingα-tubulin acetyltransferase 1(ATAT1),a newly discoveredα-tubulin acetyltransferase,decreased Ac-α-tub levels and enhanced the erythrophagocytosis by BV2 and RAW264.7 cells.Consistent with these findings,in ATAT1-/-mice,we observed increased ionized calcium binding adapter molecule 1(Iba1)and Perls-positive microglia/macrophage phagocytes of red blood cells in peri-hematoma and reduced hematoma volume in mice with intracerebral hemorrhage.Additionally,knocking out ATAT1 alleviated neuronal apoptosis and pro-inflammatory cytokines and increased anti-inflammatory cytokines around the hematoma,ultimately improving neurological recovery of mice after intracerebral hemorrhage.These findings suggest that ATAT1 deficiency accelerates erythrophagocytosis by microglia/macrophages and hematoma absorption after intracerebral hemorrhage.These results provide novel insights into the mechanisms of hematoma clearance and suggest ATAT1 as a potential target for the treatment of intracerebral hemorrhage.
基金National Natural Science Foundation of China(No.81971220)Science and Technology Administration of Nanchong(No.19SXHZ0103).
文摘Background Epilepsy affects over 70 million people worldwide;however,the underlying mechanisms remain unclear.MicroRNAs(miRNAs)have essential functions in epilepsy.miRNA-9,a brain-specific/enriched miRNA,plays a role in various nervous system diseases and tumors,but whether miRNA-9 is involved in epilepsy and glioma-associated epilepsy remains unknown.Therefore,we aimed to explore the potential role of miR-9-5p in seizures and its effect on the survival of glioma patients,in order to provide new targets for the treatment of epilepsy and glioma.Methods The YM500v2 database was used to validate the expression of hsa-miR-9-5p in tissues.Moreover,qRT-PCR was performed to investigate the expression of miR-9-5p in temporal lobe epilepsy patients and rats with lithium-pilocarpine-induced seizures.Recombinant adeno-associated virus containing miR-9-5p was constructed to overexpress miR-9-5p in vivo.The effects of miR-9-5p on the behavior and electroencephalographic activities of the lithium-pilocarpine rat model of epilepsy were tested.Bioinformatics analysis was used to predict the targets of miR-9-5p and explore its potential role in epilepsy and glioma-associated epilepsy.Results The expression of miR-9-5p increased at 6 h and 7 days after lithium-pilocarpine-induced seizures in rats.Overexpression of miR-9-5p significantly shortened the latency of seizures and increased seizure intensity at 10 min and 20 min after administration of pilocarpine(P<0.05).Predicted targets of miR-9-5p were abundant and enriched in the brain,and affected various pathways related to epilepsy and tumor.Survival analysis revealed that overexpression of miR-9-5p significantly improved the survival of patients from with low-grade gliomas and glioblastomas.The involvement of miR-9-5p in the glioma-associated epileptic seizures and the improvement of glioma survival may be related to multiple pathways,including the Rho GTPases and hub genes included SH3PXD2B,ARF6,and ANK2.Conclusions miR-9-5p may play a key role in promoting epileptic seizures and improving glioma survival,probably through multiple pathways,including GTPases of the Rho family and hub genes including SH3PXD2B,ARF6 and ANK2.Understanding the roles of miR-9-5p in epilepsy and glioma and the underlying mechanisms may provide a theoretical basis for the diagnosis and treatment of patients with epilepsy and glioma.
