Browsing by Subject "HMGB1"

Now showing 1 - 3 of 3
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    Local extension of HMGB1 in atherosclerotic lesions of human main cerebral and carotid arteries
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Umahara, T.; Uchihara, T.; Koyama, S.; Hashimoto, T.; Akimoto, J.; Haraoka, J.; Iwamoto, T.
    High mobility group box 1 protein (HMGB1) is a non-histone chromosomal protein which is highly conserved, ubiquitous, and widely distributed. HMGB1 has multiple functions in the nucleus, including the maintenance of nucleosome structure, the regulation of gene transcription, and involvement in DNA recombination. HMBG1 is currently recognized to have a wide range of potential functions and pathological relevance. HMGB1 is released into the extracellular space from necrotic cells and from activated macrophages. HMGB1 binds to the receptor for advanced glycation end products, resulting in the induction of inflammatory cytokines, and to endothelial cell thrombomodulin. HMGB1 neutralization may also reduce the development of atherosclerosis and ameliorate brain infarction. We investigated the immunolocalization of HMGB1 in atherosclerotic lesions of human cerebral and carotid arteries using a specific antibody, and confirmed the detailed expression and cell type localization using double immunofluorolabeling. In the main cerebral arteries, this anti-HMGB1 antibody intensely immunolabeled both normal morphological vascular smooth muscle cells (VSMCs) within the tunica media and infiltrating VSMCs within the intima of thickened fibrous cap plaques. Endothelial cells were also positive for HMGB1. In carotid plaques, HMGB1-like immunoreactivity (IR) was intense in macrophages, although this IR decreased with increasing cell size. Medium-sized foam cells (50-150 µm) were the most intensely stained. This IR was also observed in the nuclei of foam cells and VSMCs. These findings may provide a basis for understanding the association of HMGB1 with atherosclerotic lesions of the cerebral and carotid arteries, and for constructing strategies to counteract atherosclerosis with anti-HMGB1 antibody.
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    miR-590-3p protects against ischaemia/reperfusion injury in an oxygen-glucose deprivation and reoxygenation cellular model by regulating HMGB1/TLR4/MyD88/NF-κB signalling
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wang, Yaping; Jin, Fanfu; Huang, Lanxiu; Wu, Wenqian; Hu, Wenjie; Huang, Tingting; Ma, Lingsong; Chu, Zhaohu; Xu, Yang; Zhao, Shou-cai
    miR-590-3p has been reported to be reduced in myocardial ischaemia-reperfusion (I/R) injury, but its specific role in cerebral I/R injury is still uncertain. Thus, we explored the function and mechanism of miR590-3p in cerebral I/R injury using a cellular model. miR-590-3p, high mobility group Box 1 (HMGB1), and signalling-related factor levels were assessed using qPCR or a western blot analysis. Cell apoptosis was measured by flow cytometry. Inflammatory factors were detected by ELISA. The target of miR-590-3p was confirmed by dual-luciferase reporter assay and western blot analysis. We found that miR-590-3p was decreased and HMGB1 was increased in the OGD/R model. Upregulation of miR-590-3p reduced cell apoptosis and inflammation in the OGD/R model, and the TLR4/MyD88/NF-κB signalling pathway was suppressed. However, inhibition of miR-590-3p showed the opposite effects. Moreover, HMGB1 was verified as a target gene of miR-590-3p. HMGB1 reversed the decrease in apoptosis and inflammation caused by overexpression of miR590-3p, and the TLR4/MyD88/NF-κB signalling pathway was activated. Our results suggest that miR-590-3p regulates the TLR4/MyD88/NF-κB pathway by interacting with HMGB1 to protect against OGD/R-induced I/R injury. Thus, miR-590-3p may serve as a potential therapeutic target in cerebral I/R repair.
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    Time-dependent and lesion-dependent HMGB1-selective localization in brains of patients with cerebrovascular diseases
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Umahara, Takahiko; Uchihara, Toshiki; Hirokawa, Katsuiku; Hirao, Kentaro; Shimizu, Soichiro; Hashimoto, Takao; Terasi, Hiroo; Hanyu, Haruo
    High mobility group box 1 protein (HMGB1) has multiple functions, including the maintenance of nucleosomes and the regulation of gene transcription. HMGB1 is released from activated macrophages, resulting in the induction of inflammatory cytokines. Recently, much research about the role of HMGB1 in cerebrovascular disease (CVD) has been reported. In an animal model, HMGB1 neutralization ameliorates brain infarction, there is an early release of HMGB1 from neurons, and HMGB1 antibody attenuates delayed cerebral vasospasm in experimental subarachnoid hemorrhage. It was also reported that elevation of HMGB1 in serum correlates with severity of acute intracerebral hemorrhage. However, the evidence of HMGB1 localization in brains of patients with CVD is very limited. Therefore, we investigated at autopsy the immunolocalization of HMGB1 in brains of patients with CVD (acute and chronic cerebral infarction, acute cerebral hemorrhage, subarachnoid hemorrhage). In 3 out of 10 acute cerebral infarction cases, the cytoplasm of neurons located around the ischemic core (i.e., penumbra) was positive for HMGB1. In the chronic stage of cerebral infarction, macrophages located in some ischemic regions were positive for HMGB1. Around the hematoma in the basal ganglia, HMGB1-like immunoreactivity (IR) was intense in macrophages. However, around the subarachnoid hematoma, HMGB1- like IR was not seen in the cortex. In arteries surrounded by subarachnoid hematoma, HMGB1-like IR was located in the cytoplasm of vascular smooth muscle cells. These findings, which partially differ from animal model results, may provide translational research and a basis for understanding the role of HMGB1 in brains of patients with CVD.