Microglial V-set and immunoglobulin domain-containing 4 protects against ischemic stroke in mice by suppressing TLR4-regulated inflammatory response

Lyu, Qingping; Pang, Xiaojun; Zhang, Zibin; Wei, Yuyu; Hong, Jinxu; Chen, Huai

doi:10.1016/j.bbrc.2019.11.077

Cited by 19 publications

(11 citation statements)

References 27 publications

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“…CRIg, also expressed by microglia, is downregulated after stroke, reaching its lowest expression at 3 days post injury. Overexpression of CRIg prior to MCAO or oxygen-glucose deprivation is neuroprotective, reducing ischemic volume, preventing TLR-4induced inflammation, and attenuating neuronal loss [231].…”

Section: Strokementioning

confidence: 99%

The good, the bad, and the opportunities of the complement system in neurodegenerative disease

Schartz

Tenner

2020

J Neuroinflammation

173

183

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The complement cascade is a critical effector mechanism of the innate immune system that contributes to the rapid clearance of pathogens and dead or dying cells, as well as contributing to the extent and limit of the inflammatory immune response. In addition, some of the early components of this cascade have been clearly shown to play a beneficial role in synapse elimination during the development of the nervous system, although excessive complement-mediated synaptic pruning in the adult or injured brain may be detrimental in multiple neurogenerative disorders. While many of these later studies have been in mouse models, observations consistent with this notion have been reported in human postmortem examination of brain tissue. Increasing awareness of distinct roles of C1q, the initial recognition component of the classical complement pathway, that are independent of the rest of the complement cascade, as well as the relationship with other signaling pathways of inflammation (in the periphery as well as the central nervous system), highlights the need for a thorough understanding of these molecular entities and pathways to facilitate successful therapeutic design, including target identification, disease stage for treatment, and delivery in specific neurologic disorders. Here, we review the evidence for both beneficial and detrimental effects of complement components and activation products in multiple neurodegenerative disorders. Evidence for requisite co-factors for the diverse consequences are reviewed, as well as the recent studies that support the possibility of successful pharmacological approaches to suppress excessive and detrimental complement-mediated chronic inflammation, while preserving beneficial effects of complement components, to slow the progression of neurodegenerative disease.

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Section: Strokementioning

confidence: 99%

The good, the bad, and the opportunities of the complement system in neurodegenerative disease

Schartz

Tenner

2020

J Neuroinflammation

173

183

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“…Some genes whose transcripts were elevated by burn injury in this study have been shown to cluster into well-characterised regulons. The TLR4/MyD88 regulon is known to regulate production of ROS, immunosuppression and chronic inflammation in response to lipopolysaccharide challenge via NOX4, ARG1 and CCL2, 50 – 52 three genes whose burn trauma-induced elevations were not reversed by nephrilin in the current study. One possible line of investigation suggested by this result is co-treatment of thermal insult with both nephrilin and a modifier of TLR4 signalling such as fenofibric acid.…”

Section: Discussionmentioning

confidence: 55%

Transcriptional re-programming in rat central nervous system two weeks after burn trauma: the impact of nephrilin treatment on the expression of oxidative stress-related genes

Mascarenhas

2020

Scars, Burns & Healing

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Introduction: Survivors of severe burns suffer lifetime neuroinflammatory consequences manifested by higher incidence of major depression and neurodegenerative disease. In a scald model, nephrilin peptide has previously been shown to protect rats from loss of lean body mass, kidney function and glycaemic control, complications that have also been shown to endure in burn patient populations. Nephrilin’s mechanism of action has been suggested to involve protection from excessive oxidative stress. Methods: Using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) amplification of transcripts in total RNA extracted from dorsal root ganglia of male rats 14 days after exposure to thermal insult, we query the relative levels of expression of 34 genes believed to be associated with oxidative stress biology in the central nervous system (CNS). We use these data to explore the central role of oxidative stress in astrogliosis, immunosuppression and mitochondrial homeostasis. Results and Discussion: Rats that received nephrilin treatment (4 mg/kg by subcutaneous bolus injection once daily for seven days after scald injury) showed significantly reduced elevations in gene expression of some key genes such as NOX2, GFAP, AQP4 and RAC1, but not of others such as NOX4, STEAP4, ARG1 and CCL2. Conclusion: The implications of these data with reference to nephrilin’s potential clinical utility for mitigating the enduring effects of burn trauma on the CNS are discussed. Nephrilin reduces the expression of some genes implicated in neurodegeneration after burn insult. Lay Summary Nephrilin peptide is a novel treatment for short- and long-term systemic effects of burn trauma. This study measures the capability of nephrilin to address post-traumatic neurodegenerative disease by looking at the expression of genes in the central nervous system, in a rat scald model. Nephrilin appears to have beneficial effects by reducing the expression of some key genes known to be relevant in neurodegenerative processes, but not others.

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“…As reported by earlier studies, the content of nitric oxide is positively linked to the index of osteocyte apoptosis, indicating that nitric oxide induced osteocyte apoptosis ( Bai et al, 2015 ). Coincidentally, according to several studies, abnormal arginase expression displayed significant correlations with multiple pathological processes, such as ischemic stroke ( Lyu et al, 2020 ), cardiovascular ( Berkowitz et al, 2003 ), and immune-mediated ( Morris, 2016 ). Clemente et al (2020) also reported that arginase was considered a potential biological marker of disease severity and progression and also acted as the research subject based on the therapeutic efficacy of arginase inhibitors.…”

Section: Discussionmentioning

confidence: 99%

ARG2, MAP4K5 and TSTA3 as Diagnostic Markers of Steroid-Induced Osteonecrosis of the Femoral Head and Their Correlation With Immune Infiltration

Zhang

Zhuo

et al. 2021

Front. Genet.

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BackgroundThe diagnosis for steroid-induced osteonecrosis of the femoral head (SONFH) is hard to achieve at the early stage, which results in patients receiving ineffective treatment options and a poor prognosis for most cases. The present study aimed to find potential diagnostic markers of SONFH and analyze the effect exerted by infiltration of immune cells in this pathology.Materials and MethodsR software was adopted for identifying differentially expressed genes (DEGs) and conducting functional investigation based on the microarray dataset. Then we combined SVM-RFE, WGCNA, LASSO logistic regression, and random forest (RF) algorithms for screening the diagnostic markers of SONFH and further verification by qRT-PCR. The diagnostic values were assessed through receiver operating characteristic (ROC) curves. CIBERSORT was then adopted for assessing the infiltration of immune cells and the relationship of infiltration-related immune cells and diagnostic markers.ResultsWe identified 383 DEGs overall. This study found ARG2, MAP4K5, and TSTA3 (AUC = 0.980) to be diagnostic markers of SONFH. The results of qRT-PCR showed a statistically significant difference in all markers. Analysis of infiltration of immune cells indicated that neutrophils, activated dendritic cells and memory B cells were likely to show the relationship with SONFH occurrence and progress. Additionally, all diagnostic markers had different degrees of correlation with T cell follicular helper, neutrophils, memory B cells, and activated dendritic cells.ConclusionARG2, MAP4K5, and TSTA3 are potential diagnostic genes for SONFH, and infiltration of immune cells may critically impact SONFH occurrence and progression.

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Microglial V-set and immunoglobulin domain-containing 4 protects against ischemic stroke in mice by suppressing TLR4-regulated inflammatory response

Cited by 19 publications

References 27 publications

The good, the bad, and the opportunities of the complement system in neurodegenerative disease

The good, the bad, and the opportunities of the complement system in neurodegenerative disease

Transcriptional re-programming in rat central nervous system two weeks after burn trauma: the impact of nephrilin treatment on the expression of oxidative stress-related genes

ARG2, MAP4K5 and TSTA3 as Diagnostic Markers of Steroid-Induced Osteonecrosis of the Femoral Head and Their Correlation With Immune Infiltration

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