Analysis of IgG subclass antibodies and expression of T-Cell receptor signaling molecules in anti-CD4 monoclonal antibody treated mice with autoimmune cardiomyopathy

Wang, Zhaohui; Liao, Yuhua; Yuan, Jing; Zhang, Jinghui; Liu, Zhongping; Dong, Jing

doi:10.1080/08916930600845915

Cited by 4 publications

(3 citation statements)

References 31 publications

(27 reference statements)

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“…CXCL9 and CXCL10 are the main regulators of myocardial inflammatory cell migration and associated to the risk of DCM 32 . Apart from these, LCK, ZAP-70 and APLNR are also found to be associated with DCM 33 , 34 . TFs are proteins that play important roles in human diseases by binding to specific DNA sequence and regulating the transcription of related genes 35 .…”

Section: Discussionmentioning

confidence: 96%

Integrated bioinformatics analysis for identifying key genes and pathways in female and male patients with dilated cardiomyopathy

Zhang

Wang

Chen

et al. 2023

Sci Rep

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Dilated cardiomyopathy (DCM) is a common cause of heart failure, and males are more likely to suffer from DCM than females. This research aimed at exploring possible DCM-associated genes and their latent regulatory effects in female and male patients. WGCNA analysis found that in the yellow module, 341 and 367 key DEGs were identified in females and males, respectively. A total of 22 hub genes in females and 17 hub genes in males were identified from the PPI networks of the key DEGs based on Metascape database. And twelve and eight potential TFs of the key DEGs were also identified in females and males, respectively. Eight miRNAs of 15 key DEGs were screened in both females and males, which may be differentially expressed in females and males. Dual-luciferase reporter assay demonstrated that miR-21-5P could directly target the key gene MATN2. Furthermore, Sex differences in KEGG pathways were identified. Both KOBAS and GSEA analysis identified 19 significantly enriched pathways related to immune response in both females and males, and the TGF-β signaling pathway was exclusively identified in males. Network pharmacology analysis revealed that seven key DEGs were potential targets for the treatment of DCM, of which the OLR1 gene was only identified in males, the expression levels of the seven genes were verified by RT-PCR. The above results could offer a novel understanding of sex differences in key genes and pathways in DCM progression.

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Section: Discussionmentioning

confidence: 96%

Integrated bioinformatics analysis for identifying key genes and pathways in female and male patients with dilated cardiomyopathy

Zhang

Wang

Chen

et al. 2023

Sci Rep

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“…Additionally, WNT signaling is a critical pathway for cardiac hypertrophy and remodeling (Bergmann, 2010;Malekar et al, 2010;Lu et al, 2016). CD4+ T-cells may play a critical role in ADP/ATP carrier-caused mouse DCM (Wang et al, 2006). Inflammatory endothelial activation and migration of immunocompetent cells have been observed in 67% of DCM patients, a process mediated by cell adhesion (Noutsias et al, 1999(Noutsias et al, , 2003.…”

Section: Discussionmentioning

confidence: 99%

Differential Expression Profiles and Functional Prediction of Circular RNAs in Pediatric Dilated Cardiomyopathy

Sun

Han

Cai

et al. 2020

Front. Mol. Biosci.

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Circular RNAs (circRNAs) have emerged as essential regulators and biomarkers in various diseases. To assess the different expression levels of circRNAs in pediatric dilated cardiomyopathy (PDCM) and explore their biological and mechanistic significance, we used RNA microarrays to identify differentially expressed circRNAs between three children diagnosed with PDCM and three healthy age-matched volunteers. The biological function of circRNAs was assessed with a circRNA–microRNA (miRNA)–mRNA interaction network constructed from Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Differentially expressed circRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in 25 children with PDCM and 25 healthy volunteers. We identified 257 up-regulated (fold change ≤ 0.5, P < 0.05) and 899 down-regulated (fold change ≥2, P < 0.05) circRNAs in PDCM patients when compared to healthy volunteers. The qRT-PCR experiments confirmed has_circ_0067735 down-regulation (0.45-fold, P < 0.001), has_circ_0070186 up-regulation (2.82-fold, P < 0.001), and has_circ_0069972 down-regulation (0.50-fold, P < 0.05). A functional analysis of these differentially expressed circRNAs suggests that they are associated with hypertrophy, remodeling, fibrosis, and autoimmunity. CircRNAs have been implicated in PDCM through largely unknown mechanisms. Here we report differentially expressed circRNAs in PDCM patients that may illuminate the mechanistic roles in the etiology of PDCM that could serve as non-invasive diagnostic biomarkers.

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“…This anti-CD4 antibody acts by causing the accumulation of CD4 molecules inside membrane rafts and by excluding the ZAP-70 kinase and the downstream targets SLP-76, PLC 1 and Vav from the raft machinery. Impaired recruitment of the TCR/CD3 complex, p56Lck kinase and downstream signaling molecules, and reduced phosphorylation of CD3, ZAP-70, LAT, SLP-76 and Vav [176,177], or TCR transgenic Rag +/+ mice [178]. Impaired recruitment of the TCR/CD3 complex, p56Lck kinase and downstream signaling molecules, and reduced phosphorylation of CD3, ZAP-70, LAT, SLP-76 and Vav [176,177], or TCR transgenic Rag +/+ mice [178].…”

Section: Anti-cd4 Antibodies To Disrupt the Lipid-protein Rheostat Inmentioning

confidence: 99%

Targeting CD4 to Disrupt Signaling Through Membrane Rafts: Towards a Raft-Based Therapeutics

Chentouf¹,

Rigo²,

Pèlegrin³

et al. 2008

IEMAMC

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Membrane rafts, due to the presence of several immunoreceptors, signal-transducing kinases and lipids such as ceramides which can act as second messengers, play a crucial role in the cell signaling network which fine-tunes various biological effects. The ability of membrane rafts to segregate receptors provides a mechanism for compartmentalization of signaling molecules in plasma membrane by concentrating some components in membrane rafts and excluding others. Based on these observations, the concept of raft-based therapeutics has recently emerged. Raft-targeting molecules can modulate the lipid-protein rheostat of membrane rafts to treat various diseases, such as cancer, neurological disorders or infectious diseases. In this review, we focus on membrane rafts as "discrete" organizing elements of T lymphocytes' plasma membrane and how to reconcile the dynamic nature of membrane rafts with the formation of the immunological synapse. We describe CD4-specific antibodies as prototypical modulators for the disruption of the lipid-protein rheostat in membrane rafts and extend the concept of raft-based therapeutics to other antibodies, sterol-and sphingolipid-modulating drugs, glycerophospholipid analogs, fatty acid modulators, and peptide-derived molecules. This review highlights a novel mode of action of drugs through dietary or therapeutic interventions that target membrane rafts.

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Analysis of IgG subclass antibodies and expression of T-Cell receptor signaling molecules in anti-CD4 monoclonal antibody treated mice with autoimmune cardiomyopathy

Cited by 4 publications

References 31 publications

Integrated bioinformatics analysis for identifying key genes and pathways in female and male patients with dilated cardiomyopathy

Integrated bioinformatics analysis for identifying key genes and pathways in female and male patients with dilated cardiomyopathy

Differential Expression Profiles and Functional Prediction of Circular RNAs in Pediatric Dilated Cardiomyopathy

Targeting CD4 to Disrupt Signaling Through Membrane Rafts: Towards a Raft-Based Therapeutics

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