The Effect of Osteopontin on Microglia

Yu, Hui; Liu, Xiaohong; Zhong, Yisheng

doi:10.1155/2017/1879437

Cited by 51 publications

(46 citation statements)

References 74 publications

(87 reference statements)

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“…SPP1 has been nominated as an AD CSF biomarker in previous studies [106][107][108][109] . SPP1 is known to be involved in tissue repair 110 , and promotes phagocytosis of amyloid-β and an anti-inflammatory microglial phenotype 111,112 . It is closely associated with the CD44 receptor 113 , which is highly expressed on the surface of activated astrocytes 114 .…”

Section: Discussionmentioning

confidence: 99%

A Consensus Proteomic Analysis of Alzheimer’s Disease Brain and Cerebrospinal Fluid Reveals Early Changes in Energy Metabolism Associated with Microglia and Astrocyte Activation

Johnson

Dammer

Duong

et al. 2019

Preprint

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Our understanding of the biological changes in the brain associated with Alzheimer's disease (AD) pathology and cognitive impairment remains incomplete. To increase our understanding of these changes, we analyzed dorsolateral prefrontal cortex of control, asymptomatic AD, and AD brains from four different centers by label-free quantitative mass spectrometry and weighted protein co-expression analysis to obtain a consensus protein co-expression network of AD brain.This network consisted of 13 protein co-expression modules. Six of these modules correlated with amyloid-β plaque burden, tau neurofibrillary tangle burden, cognitive function, and clinical functional status, and were altered in asymptomatic AD, AD, or in both disease states. These modules reflected synaptic, mitochondrial, sugar metabolism, extracellular matrix, cytoskeletal, and RNA binding/splicing biological functions. The identified protein network modules were preserved in a community-based cohort analyzed by a different quantitative mass spectrometry approach. They were also preserved in temporal lobe and precuneus brain regions. Some of the modules were influenced by aging, and showed changes in other neurodegenerative diseases such as frontotemporal dementia and corticobasal degeneration. The module most strongly associated with AD pathology and cognitive impairment was the sugar metabolism module, which was enriched in AD genetic risk factors and correlated with APOE genetic risk. This module was also highly enriched in microglia and astrocyte protein markers associated with an antiinflammatory state, suggesting that the biological functions it represents serve a protective role in AD. Proteins from this module were increased in cerebrospinal fluid from asymptomatic AD and AD cases, highlighting their potential as biomarkers of the altered brain network. In this study of >2000 brains and nearly 400 cerebrospinal fluid samples by quantitative proteomics, we identify proteins and biological processes in AD brain that may serve as therapeutic targets and fluid biomarkers for the disease. IntroductionAlzheimer's disease (AD) is a leading cause of death worldwide, with increasing prevalence as global life expectancy increases 1 . Although AD is currently defined on the basis of amyloid-β plaque and tau neurofibrillary tangle deposition within the neocortex 2 , the biochemical and cellular changes in the brain that characterize the disease beyond amyloid-β and tau deposition remain incompletely understood. The genetic architecture of late-onset AD has been extensively studied, and the results of these studies implicate multiple biological pathways that contribute to development of the disease, including immune function, endocytic vesicle trafficking, and lipid homeostasis, among others 3-5 . In addition to genetic studies, transcriptomic studies on postmortem AD brain tissue have identified changes in mRNA co-expression that correlate with disease traits and cognitive decline 6,7 . However, given that mRNA levels correlate only modestly to protein le...

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Section: Discussionmentioning

confidence: 99%

A Consensus Proteomic Analysis of Alzheimer’s Disease Brain and Cerebrospinal Fluid Reveals Early Changes in Energy Metabolism Associated with Microglia and Astrocyte Activation

Johnson

Dammer

Duong

et al. 2019

Preprint

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“…S8). The lesion 1 cluster was also characterized by an increase in Spp1, or osteopontin, which is an extracellular matrix (ECM) protein that can promote microglia survival (16), and the chemokine Cxcl2. Cells in the lesion 1 cluster cells also expressed the lysosomal Lyz2, and Cd74, which play a role in the intracellular sorting of major histocompatibility complex II (17).…”

Section: Single-cell Transcriptional Profiling Of Microglia Activatiomentioning

confidence: 99%

Microglia response following acute demyelination is heterogeneous and limits infiltrating macrophage dispersion

et al. 2020

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Microglia and infiltrating macrophages are thought to orchestrate the central nervous system (CNS) response to injury; however, the similarities between these cells make it challenging to distinguish their relative contributions. We genetically labeled microglia and CNS-associated macrophages to distinguish them from infiltrating macrophages. Using single-cell RNA sequencing, we describe multiple microglia activation states, one of which was enriched for interferon associated signaling. Although blood-derived macrophages acutely infiltrated the demyelinated lesion, microglia progressively monopolized the lesion environment where they surrounded infiltrating macrophages. In the microglia-devoid sciatic nerve, the infiltrating macrophage response was sustained. In the CNS, the preferential proliferation of microglia and sparse microglia death contributed to microglia dominating the lesion. Microglia ablation reversed the spatial restriction of macrophages with the demyelinated spinal cord, highlighting an unrealized macrophages-microglia interaction. The restriction of peripheral inflammation by microglia may be a previously unidentified mechanism by which the CNS maintains its “immune privileged” status.

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“…Osteopontin (OPN) is considered a key cytokine in cellular immune response and may also regulate inflammation (7,8). OPN concentration is elevated in central nervous system lesions in ischemic and traumatic brain injuries, indicating that it may contribute to the neuropathology in neurodegenerative diseases (9,10). One possible mechanism may be related to OPN's capacity to directly modulate the cytokine expression and survival of microglia (11).…”

Section: Introductionmentioning

confidence: 99%

Elevated Osteopontin and Interferon Gamma Serum Levels and Increased Neutrophil-to-Lymphocyte Ratio Are Associated With the Severity of Symptoms in Schizophrenia

et al. 2020

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Inflammation and immune dysregulation could contribute to the pathogenesis of schizophrenia. Osteopontin (OPN) is a cytokine-like glycoprotein involved in inflammation and in modulating immune responses, and it can also directly modify the cytokine expression and survival of microglia. Furthermore, elevated gene expression of OPN in first episode psychosis has recently been described, but to date OPN level has not been investigated in schizophrenia. Imbalance of T-helper subtypes could also represent a vulnerability factor for schizophrenia. In this study, we analyzed the concentration of OPN, levels of cytokines associated with T-helper subtypes: interferon gamma (IFNy) for Th1, interleukin (IL)-10 for Th2, IL-8 for Th17, and neutrophil-to-lymphocyte ratio (NLR) in 22 patients with schizophrenia assessed for the intensity of their symptoms by the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression scale (CGI) scores. Serum OPN, IFNy, IL-10, and IL-8 concentrations were measured by ELISA kits and NLR was calculated from blood count. We found significant correlation between the level of OPN and PANSS-total and PANSS-general scores. IFNy level and NLR showed significant correlation with PANSS-total, PANSS-positive, PANSS-general, and CGI score. Among the measured markers antipsychotic therapy only had significant effects on NLR and OPN level, both of which were significantly reduced after long-term antipsychotic treatment. Our results indicate that elevated OPN and IFNy concentrations, and increased NLR are associated with severe symptoms in schizophrenia and suggest the importance of Th1 subtype in patients with high PANSS-positive and PANSS-general subscore. Significant correlation between NLR and PANSS scores strengthens the inflammation hypothesis of schizophrenia.

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The Effect of Osteopontin on Microglia

Cited by 51 publications

References 74 publications

A Consensus Proteomic Analysis of Alzheimer’s Disease Brain and Cerebrospinal Fluid Reveals Early Changes in Energy Metabolism Associated with Microglia and Astrocyte Activation

A Consensus Proteomic Analysis of Alzheimer’s Disease Brain and Cerebrospinal Fluid Reveals Early Changes in Energy Metabolism Associated with Microglia and Astrocyte Activation

Microglia response following acute demyelination is heterogeneous and limits infiltrating macrophage dispersion

Elevated Osteopontin and Interferon Gamma Serum Levels and Increased Neutrophil-to-Lymphocyte Ratio Are Associated With the Severity of Symptoms in Schizophrenia

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