FABP4 activates the JAK2/STAT2 pathway via Rap1a in the homocysteine-induced macrophage inflammatory response in ApoE   mice atherosclerosis

Xu, Lingbo; Zhang, Huiping; Wang, Yanhua; Ai, Yang; Dong, Xiaoyan; Gu, Lingyu; Liu, Dayue; Ding, Ning; Jiang, Yideng

doi:10.1038/s41374-021-00679-2

Cited by 25 publications

(23 citation statements)

References 50 publications

(49 reference statements)

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“…Here, we identified eight DEGs, including JAK2, ORM1, RNASE2, TNFSF13B, CYBB, EIF2AK2, CD79B and CAMP . More recently, increased interest in JAKi strategies arose for the need of potential treatments for COVID-19, which is implicated in the activation of CD4 + and CD8 + positive T cells, NK cells and monocytes that cooperate with cytokine storm generated by SARS-COV2 ( 46 , 47 ). Two molecules are mainly under focus of pharmaceutical industry, baricitinib and ruxolitinib ( 23 , 48 ).…”

Section: Discussionmentioning

confidence: 99%

“…In TFs-mRNA network, JAK2 and STAT2 mediate the signal transduction of more than 50 cytokines and growth factors in many different cell types, which is critical for resisting infection and enforcing barrier functions. JAK2/STAT2 pathway contributes to homocysteine-accelerated macrophage inflammation, adding to the risk for atherosclerosis ( 46 ).…”

Section: Discussionmentioning

confidence: 99%

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Integrated bioinformatics analysis identifies shared immune changes between ischemic stroke and COVID 19

Liu

Han²,

Wan³

et al. 2023

Front. Immunol.

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Although COVID-19 is primarily a respiratory disease, its neurological complications, such as ischemic stroke (IS), have aroused growing concerns and reports. However, the molecular mechanisms that underlie IS and COVID-19 are not well understood. Therefore, we implemented transcriptomic analysis from eight GEO datasets consist of 1191 samples to detect common pathways and molecular biomarkers in IS and COVID-19 that help understand the linkage between them. Differentially expressed genes (DEGs) were detected for IS and COVID-19 separately for finding shared mechanisms and we found that immune-related pathways were outlined with statistical significance. JAK2, which was identified as a hub gene, was supposed to be a potential therapeutic gene targets during the immunological process of COVID-19 and IS. Besides, we found a decrease in the proportion of CD8+ T and T helper 2 cells in the peripheral circulation of both COVID and IS patients, and NCR3 expression was significantly correlated with this change. In conclusion, we demonstrated that transcriptomic analyses reported in this study could make a deeper understanding of the common mechanism and might be promising for effective therapeutic for IS and COVID-19.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis identifies shared immune changes between ischemic stroke and COVID 19

Liu

Han²,

Wan³

et al. 2023

Front. Immunol.

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“…Inhibition of FABP4 in wound macrophages reduces inflammatory cytokine expression, making FABP4 a potent regulatory target for excessive inflammation and wound repair in diabetic patients [ 6 ]. FABP4 plays an important role in macrophage inflammation and lipid metabolism in atherosclerosis [ 3 ]. So its role in cancer may also be associated with macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…Elevated plasma FABP4 concentrations were associated with a slightly higher risk of heart failure in American older adults in a prospective study of 4179 participants [ 2 ]. FABP4 plays an important role in macrophage inflammation and lipid metabolism in atherosclerosis [ 3 ], and serum FABP4 is strongly associated with cardiovascular disease mortality [ 4 ]. Therefore, the pathogenic cause may be related to endoplasmic reticulum stress [ 5 ] and inflammatory cytokines in macrophages [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Diagnostic, Prognostic, and Immunological Roles of FABP4 in Pancancer: A Bioinformatics Analysis

Yang

Liu

Shao

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. Fatty acid binding protein 4 (FABP4) is mainly involved in the regulation of systemic metabolism through various lipid signaling pathways. Metabolic reprogramming is one of the important factors in the development and progression of cancer. It has been recently reported that FABP4 is closely related to the development of cancer and may be involved in tumor invasion and metastasis. Methods. In this study, we explored the expression pattern of FABP4 in pancancer through TCGA and CPTAC. Using TCGA, Kaplan-Meier Plotter, and STRING databases, to explore its diagnostic and prognostic value, and function through GO/KEGG and GSEA. Then, using the TIMER2.0 database, we investigated the correlation between FABP4 expression and immune infiltration in cancers, especially stomach adenocarcinomas (STAD) and colorectal adenocarcinoma (COADREAD). Results. Compared with normal tissues, the expression of FABP4 in more than 10 tumor tissues was lower ( p < 0.05 ). Through the receiver operating characteristic (ROC) curve, the diagnostic value was found higher in colorectal cancer, breast cancer, thyroid cancer, and lung cancer, with the area under the curve AUC > 0.9 . Through the K-M curve, FABP4 was found to correlate to the prognosis of various cancers. The results of gastric cancer and colorectal cancer are consistent. The low-expression group has a better prognosis than the high-expression group, and the expression of FABP4 in the early T and N stages of gastrointestinal tumors is lower. FABP4 highly expressed gene set is mostly enriched in extracellular matrix degradation and cell adhesion functions. Gastrointestinal tumors with high expression of FABP4 may have more immunosuppressive effects on macrophages and have a worse prognosis. Conclusion. FABP4 can be used as a diagnostic and prognostic biomarker in pancancer, and its high expression in gastrointestinal tumors suggests poor prognosis. This may be correlated to the immune infiltration of macrophages and epithelial-mesenchymal transition.

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“…All functional subsets of RA CD8 expressed CD36 more often, as well as FABP4 and GPR84, than CNT, and the cell surface expression of FABP4 and GPR84 were especially higher in RA effector and memory subsets. In mice, macrophages polarize towards a pro-inflammatory phenotype upon activation of the JAK/STAT-pathway by FABP4, while an agonist of GPR84 triggered TNF-α production in human peripheral blood mononuclear cells [30,31]. These studies may explain the decrease in the expression of these two transporters in RA patients receiving JAK inhibitor or TNF-blockade therapies.…”

Section: Discussionmentioning

confidence: 99%

Reduction of pro-inflammatory effector functions through remodeling of fatty acid metabolism in CD8⁺ T-cells from Rheumatoid Arthritis patients

Kraus

Keck

Klika

et al. 2022

Preprint

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Objectives: RA CD8+ T-cells (CD8) maintain their effector pro-inflammatory phenotype by changing their metabolism towards aerobic glycolysis. However, their massive energetic and biosynthetic needs may require additional substrates to furnish this high demand. Since systemic alterations in lipid metabolism have been reported in RA patients, we explored the role of fatty acid (FA) metabolism in CD8 to identify potential targets to curb their pro-inflammatory potential. Methods: The expression of FA metabolism-related genes was analyzed for total and CD8-subsets from RA patients and healthy controls (CNT). Peripheral-blood CD8 were isolated from RA, PsA, SpA patients under different therapies (DMARD, biologicals, JAK-inhibitors) and CNT and were TCR-stimulated with or without FA metabolism inhibitors. We quantified the expression of the main FA transporters, lipid uptake, intracellular content of (un-)saturated FA, cytokine production, activation, proliferation, and capacity to inhibit tumor cell growth. Results: The CD8 gene expression profile of FA metabolism-related genes was significantly different between untreated RA patients and CNT. RA patients with a good clinical response after 6 months MTX therapy significantly increased the expression of FA metabolism-related genes. Cell-surface expression of FA transporters FABP4 and GPR84 and FA-uptake was higher in effector and memory CD8 of RA patients than for CNT. In vitro blockade of FA metabolism significantly impaired CD8 effector functions. Conclusions: RA CD8 present an altered FA-metabolism which can be potential therapeutic targets to control their pro-inflammatory profile, especially by targeting the transport and oxidation of free FAs which are abundant in the serum and synovial fluid of patients.

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FABP4 activates the JAK2/STAT2 pathway via Rap1a in the homocysteine-induced macrophage inflammatory response in ApoE mice atherosclerosis

Cited by 25 publications

References 50 publications

Integrated bioinformatics analysis identifies shared immune changes between ischemic stroke and COVID 19

Integrated bioinformatics analysis identifies shared immune changes between ischemic stroke and COVID 19

Diagnostic, Prognostic, and Immunological Roles of FABP4 in Pancancer: A Bioinformatics Analysis

Reduction of pro-inflammatory effector functions through remodeling of fatty acid metabolism in CD8⁺ T-cells from Rheumatoid Arthritis patients

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FABP4 activates the JAK2/STAT2 pathway via Rap1a in the homocysteine-induced macrophage inflammatory response in ApoE mice atherosclerosis

Cited by 25 publications

References 50 publications

Integrated bioinformatics analysis identifies shared immune changes between ischemic stroke and COVID 19

Integrated bioinformatics analysis identifies shared immune changes between ischemic stroke and COVID 19

Diagnostic, Prognostic, and Immunological Roles of FABP4 in Pancancer: A Bioinformatics Analysis

Reduction of pro-inflammatory effector functions through remodeling of fatty acid metabolism in CD8+ T-cells from Rheumatoid Arthritis patients

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Product

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Reduction of pro-inflammatory effector functions through remodeling of fatty acid metabolism in CD8⁺ T-cells from Rheumatoid Arthritis patients