Post-stroke administration of H2 relaxin reduces functional deficits, neuronal apoptosis and immune cell infiltration into the mouse brain

Truong, Shirley; Bonnici, Benjamin; Rupasinghe, Samoda; Kemp-Harper, Barbara K; Samuel, Chrishan S.; Broughton, Brad R.S.

doi:10.1016/j.phrs.2022.106611

Cited by 5 publications

(4 citation statements)

References 51 publications

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“…These numerous effects of relaxin are consistent with the expression pattern of its cognate receptor, RXFP1 239, 245, 246 . Notably, despite some early mapping studies of RXFP1 mRNA and binding sites in several tissues including the heart and brain, 215,247,248 few studies have explored the role of relaxin/RXFP1 signaling in brain function 249–252 …”

Section: Insulin‐like (Relaxin)‐family Peptide and Receptor Systemsmentioning

confidence: 68%

“…239,245,246 Notably, despite some early mapping studies of RXFP1 mRNA and binding sites in several tissues including the heart and brain, 215,247,248 few studies have explored the role of relaxin/RXFP1 signaling in brain function. [249][250][251][252] The INSL3/RXFP2 system was initially identified as having a clear role in male reproduction, specifically in the development of the gubernaculum and testicular descent, because INSL3 is highly expressed in testicular Leydig cells in animals and human 253 and both…”

Section: Recent Advances and Current Anatomical And Functional Knowledgementioning

confidence: 99%

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History of key regulatory peptide systems and perspectives for future research

Chen

Rehfeld

Watts

et al. 2023

J Neuroendocrinology

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Throughout the 20th Century, regulatory peptide discovery advanced from the identification of gut hormones to the extraction and characterization of hypothalamic hypophysiotropic factors, and to the isolation and cloning of multiple brain neuropeptides. These discoveries were followed by the discovery of G‐protein‐coupled and other membrane receptors for these peptides. Subsequently, the systems physiology associated with some of these multiple regulatory peptides and receptors has been comprehensively elucidated and has led to improved therapeutics and diagnostics and their approval by the US Food and Drug Administration. In light of this wealth of information and further potential, it is truly a time of renaissance for regulatory peptides. In this perspective, we review what we have learned from the pioneers in exemplified fields of gut peptides, such as cholecystokinin, enterochromaffin‐like‐cell peptides, and glucagon, from the trailblazing studies on the key stress hormone, corticotropin‐releasing factor, as well as from more recently characterized relaxin‐family peptides and receptors. The historical viewpoints are based on our understanding of these topics in light of the earliest phases of research and on subsequent studies and the evolution of knowledge, aiming to sharpen our vision of the current state‐of‐the‐art and those studies that should be prioritized in the future.

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Section: Insulin‐like (Relaxin)‐family Peptide and Receptor Systemsmentioning

confidence: 68%

Section: Recent Advances and Current Anatomical And Functional Knowledgementioning

confidence: 99%

History of key regulatory peptide systems and perspectives for future research

Chen

Rehfeld

Watts

et al. 2023

J Neuroendocrinology

View full text Add to dashboard Cite

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“…Therefore, early therapeutic interventions for TBI should aim not only to suppress microglial activation but also to modulate the microglial response to promote inflammation resolution post-injury. 9,[28][29][30] CD300LF was originally identified as a cellular receptor for noroviruses and has an important role in norovirus binding and entry into cells. 11 It's role in the CNS, particularly after brain injury, has not been thoroughly examined.…”

Section: Discussionmentioning

confidence: 99%

“…However, microglia function varies with time after TBI and across TBI models, with most activated microglia displaying a mix of pro‐ and anti‐inflammatory roles. Therefore, early therapeutic interventions for TBI should aim not only to suppress microglial activation but also to modulate the microglial response to promote inflammation resolution post‐injury 9,28‐30 …”

Section: Discussionmentioning

confidence: 99%

CD300LF⁺ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway

Lu,

Liu,

Wang

et al. 2024

CNS Neurosci Ther

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IntroductionThe diversity in microglial phenotypes and functions following traumatic brain injury (TBI) is poorly characterized. The aim of this study was to explore precise targets for improving the prognosis of TBI patients from a microglial perspective.ObjectivesTo assess whether the prognosis of TBI can be improved by modulating microglia function.ResultsIn CD300LF‐deficient mice, we observed an increase in glial cell proliferation, more extensive neuronal loss, and worsened neurological function post‐TBI. Transcriptomic comparisons between CD300LF‐positive and CD300LF‐negative microglia illuminated that the neuroprotective role of CD300LF is principally mediated by the inhibition of the STING signaling pathway. In addition, this protective effect can be augmented using the STING pathway inhibitor C‐176.ConclusionsOur research indicates that CD300LF reduces neuroinflammation and promotes neurological recovery after TBI, and that microglia are integral to the protective effects of CD300LF in this context. In summary, our findings highlight CD300LF as a critical molecular regulator modulating the adverse actions of microglia following acute brain injury and propose a novel therapeutic approach to enhance outcomes for patients with TBI.

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Identifying immune cell infiltration and effective diagnostic biomarkers for ischemic stroke using bioinformatics analysis

Zhang,

Zheng,

Luo

et al. 2024

PLoS ONE

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Ischemic stroke (IS) is a leading cause of death and disability worldwide. Screening for marker genes in IS is crucial for its early diagnosis and improvement in clinical outcomes. In the study, the gene expression profiles in the GSE22255 and GSE37587 datasets were extracted from the public database Gene Expression Omnibus. Weighted gene co‑expression network analysis (WGCNA) was used to investigate the gene sets that were related to ubiquitination. A total of 33 ubiquitination-related differentially expressed genes (DEGs) were identified using “limma (version 3.50.0)”. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) analysis enriched multiple pathways that were closely related to IS. The correlations between the HALLMARK signaling pathways and DGEs were analyzed. Receiver operating characteristic analysis was used to validate the diagnostic value of the key genes. Among them, 16 genes were identified as hub genes. Single-sample GSEA was performed to evaluate the infiltration status of immune cells in IS. To understand the potential molecular mechanisms of the hub genes in IS, we constructed RBP-mRNA and mRNA–miRNA–lncRNA interaction networks. Additionally, we used the GeneMANIA database to create a PPI network for the signature genes to investigate their functions. As a result, there was a significant difference in the overall infiltration of immune cells between the IS and control groups. Among the 28 types of immune cells, the degree of infiltration of seven types was significantly different between the two groups (p<0.05). The expression of four types of immune cells, namely type 1 T helper cell, type 17 T helper cell, eosinophil, and mast cell, in the IS group were significantly higher than that in the control group. The expressions of DHFR2 (R = -0.575; p<0.001) and DNAAF2 (R = -0.562; p<0.001) were significantly negatively correlated with eosinophil infiltration. The PPI network demonstrated that the 16 hub genes interacted with each other. In conclusion, we identified DEGs, WGCNA modules, hub genes, enriched pathways, and infiltrating immune cells that may be closely involved in IS. Further studies are required to explore the functions of these genes.

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Post-stroke administration of H2 relaxin reduces functional deficits, neuronal apoptosis and immune cell infiltration into the mouse brain

Cited by 5 publications

References 51 publications

History of key regulatory peptide systems and perspectives for future research

History of key regulatory peptide systems and perspectives for future research

CD300LF⁺ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway

Identifying immune cell infiltration and effective diagnostic biomarkers for ischemic stroke using bioinformatics analysis

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Post-stroke administration of H2 relaxin reduces functional deficits, neuronal apoptosis and immune cell infiltration into the mouse brain

Cited by 5 publications

References 51 publications

History of key regulatory peptide systems and perspectives for future research

History of key regulatory peptide systems and perspectives for future research

CD300LF+ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway

Identifying immune cell infiltration and effective diagnostic biomarkers for ischemic stroke using bioinformatics analysis

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Product

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CD300LF⁺ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway