Syk-Targeted, a New 3-Arylbenzofuran Derivative EAPP-2 Blocks Airway Inflammation of Asthma–COPD Overlap in vivo and in vitro

Li, Shuyi; Yang, Hui; Yuan, Jing; Zhang, Ziqian; Li, Xuyu; Fang, Nan; Lin, Mingbao; Hou, Qi

doi:10.2147/jir.s310875

Cited by 9 publications

(3 citation statements)

References 31 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SYK inhibitors, such as BI 1002494 and BAY 61‐3606, may offer promising treatments for chronic and acute asthma attacks. In addition, Li et al 38 synthesized Eapp‐2, a 3‐arylbenzofuran derivative with potent anti‐inflammatory and SYK‐inhibitory properties. Eapp‐2 markedly inhibited the phosphorylation of SYK and modulated the downstream NF‐κB or NLRP3 pathways.…”

Section: The Role Of Syk In Other Inflammatory and Immune Disordersmentioning

confidence: 99%

Immunomodulatory role of spleen tyrosine kinase in chronic inflammatory and autoimmune diseases

Zhou

Zhang

et al. 2023

Immunity Inflam & Disease

View full text Add to dashboard Cite

Background The high prevalence of chronic inflammatory diseases or autoimmune reactions is a major source of concern and affects the quality of life of patients. Chronic inflammatory or autoimmune diseases are associated with many diseases in humans, including asthma, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease and cancer. Splenic tyrosine kinase (SYK) is a non–receptor tyrosine kinase that plays an important role in immune receptor signalling in immune and inflammatory responses. Methods This is a review article in which we searched for keywords “splenic tyrosine kinase”, “inflammation” and “autoimmune diseases” in published literature such as Pubmed and Web of Science to collect relevant information and then conducted a study focusing on the latest findings on the involvement of SYK in chronic inflammatory or autoimmune diseases. Results This paper reviews the regulation of Fcγ, NF–κB, B cell and T cell–related signalling pathways by SYK, which contributes to disease progression in chronic inflammatory and autoimmune diseases such as airway fibrosis, inflammatory skin disease and inflammatory bowel disease. Conclusion This paper shows that SYK plays an important role in chronic inflammatory and autoimmune diseases. syk targets hematological, autoimmune and other inflammatory diseases and therefore, inhibition of SYK expression or blocking its related pathways may provide new ideas for clinical prevention and treatment of inflammatory or autoimmune diseases.

show abstract

Section: The Role Of Syk In Other Inflammatory and Immune Disordersmentioning

confidence: 99%

Immunomodulatory role of spleen tyrosine kinase in chronic inflammatory and autoimmune diseases

Zhou

Zhang

et al. 2023

Immunity Inflam & Disease

View full text Add to dashboard Cite

show abstract

“…Spleen associated tyrosine kinase (SYK), a 72kD non-receptor protein tyrosine kinase, can trigger cell degranulation and histamine release in human basophils through FcεRI-mediated signaling pathways and is required for neutrophils to form neutrophil extracellular traps. Phosphorylated SYK binds to the ITAM, triggering its downstream inflammatory signal cascades, including NF-κB and NLRP3, while the specific SYK inhibitor, EAPP-2, significantly down-regulates the expression of NF-κB, phosphorylated-NF-κB, and NLRP3 in ACO mice and in LPS-induced RAW264.7 macrophages in vitro [ 27 ].…”

Section: Potential Biomarkers For Acomentioning

confidence: 99%

Unraveling the Pathogenesis of Asthma and Chronic Obstructive Pulmonary Disease Overlap: Focusing on Epigenetic Mechanisms

Chen

Chang

Huang

et al. 2022

Cells

View full text Add to dashboard Cite

Asthma and COPD overlap (ACO) is characterized by patients presenting with persistent airflow limitation and features of both asthma and COPD. It is associated with a higher frequency and severity of exacerbations, a faster lung function decline, and a higher healthcare cost. Systemic inflammation in COPD and asthma is driven by type 1 T helper (Th1) and Th2 immune responses, respectively, both of which may contribute to airway remodeling in ACO. ACO-related biomarkers can be classified into four categories: neutrophil-mediated inflammation, Th2 cell responses, arachidonic acid-eicosanoids pathway, and metabolites. Gene–environment interactions are key contributors to the complexity of ACO and are regulated by epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs. Thus, this review focuses on the link between epigenetics and ACO, and outlines the following: (I) inheriting epigenotypes without change with environmental stimuli, or epigenetic changes in response to long-term exposure to inhaled particles plus intermittent exposure to specific allergens; (II) epigenetic markers distinguishing ACO from COPD and asthma; (III) potential epigenetic drugs that can reverse oxidative stress, glucocorticoid insensitivity, and cell injury. Improved understanding of the epigenetic regulations holds great value to give deeper insight into the mechanisms, and clarify their implications for biomedical research in ACO.

show abstract

“…AS one of Syk inhibitors, EAPP-2 alleviates airway inflammation by decreasing NF-κB, p-NF-κB, and NLRP3. 57,58 Histone acetyltransferase KAT5 is a member of the MYST acetyltransferase family. KAT5 plays an important role in the regulation of gene transcription, DNA damage, and autophagy.…”

mentioning

confidence: 99%

Analysis of Communal Molecular Mechanism Between Chronic Obstructive Pulmonary Disease and Osteoporosis

Nie¹,

Wang²,

Zeng³

et al. 2023

COPD

View full text Add to dashboard Cite

Background: Chronic obstructive pulmonary disease (COPD) patients with osteoporosis (OP) usually experience more frequent exacerbations, worse quality of life, and heavier economic burden, however, few studies have investigated common molecular mechanisms of COPD and OP. Objective: To explore the relationship between COPD and OP through bioinformatics analysis. Methods: The miRNA microarray data of COPD and OP were retrieved from the Gene Expression Database (GEO), and the differentially expressed microRNAs (DEmiRNAs) were screened and the intersection was obtained. The Targetscan, miRDB, and miRWalk databases were used to predict the target genes of DEmiRNA, and the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the R package clusterProfiler, the STRING database was used to analyze the target protein-protein interaction network (PPI) and screens to determine the core modules and core genes. Results: Two DEmiRNAs (miR-23a-5p, miR-194-3p) have been found in COPD and OP, which have predicted 76 and 114 target genes, respectively. GO functional annotations of miR-23a-5p were significantly enriched in CD40 signaling pathway, ubiquitinconjugating enzyme activity, etc; KEGG pathways of miR-23a-5p were significantly enriched in ubiquitin-mediated proteolysis, folate biosynthesis, and regulation of actin cytoskeleton. GO function annotations of miR-194-3p were significantly enriched in T cell activation regulation, ubiquitin protein ligase activity, and DNA transcription factor binding; KEGG pathways of miR-194-3p were significantly enriched in cell adhesion molecules, intercellular tight junctions, and lysosomal pathway. PPI analysis found target coding proteins formed complex regulatory networks. Ten core genes (TP53, SRC, PXN, CHD4, SYK, TNRC6B, PML, KAT5, BRD1 and IGF2) were picked out among them, then we used the MCODE plugin found three core subnetworks. Conclusion: Two identical DEmiRNAs (miR-23a-5p, miR-194-3p) exist in the peripheral blood of COPD and OP patients, which are important biomarkers for COPD patients with OP and may represent novel targets for diagnosis and treatment of COPD patients with OP.

show abstract

Syk-Targeted, a New 3-Arylbenzofuran Derivative EAPP-2 Blocks Airway Inflammation of Asthma–COPD Overlap in vivo and in vitro

Cited by 9 publications

References 31 publications

Immunomodulatory role of spleen tyrosine kinase in chronic inflammatory and autoimmune diseases

Immunomodulatory role of spleen tyrosine kinase in chronic inflammatory and autoimmune diseases

Unraveling the Pathogenesis of Asthma and Chronic Obstructive Pulmonary Disease Overlap: Focusing on Epigenetic Mechanisms

Analysis of Communal Molecular Mechanism Between Chronic Obstructive Pulmonary Disease and Osteoporosis

Contact Info

Product

Resources

About