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The Expression of MAFB Gene in Circulating Monocytes Is Related to Chronic Inflammatory Status in T2DM Patients

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Abstract

Immune cell–mediated chronic inflammation is one of the causes of type 2 diabetes mellitus (T2DM). Therefore, identifying inflammatory markers in circulating immune cells is highly important for predicting insulin resistance (IR) and the occurrence of T2DM. In this study, we discovered that differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) from T2DM patients were associated with innate immunity and chronic inflammatory responses through bulk transcriptome sequencing (bulk RNA-seq). Gene integration analysis revealed that nine DEGs were upregulated, and receiver operating characteristic (ROC) curve analysis revealed that V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), a candidate biomarker, has a certain predictive value for T2DM. In population-based cohort studies, we found that MAFB expression was significantly upregulated in the PBMCs of T2DM patients and was significantly correlated with homeostasis model assessment of IR (HOMA-IR), tumor necrosis factor-α (TNF-α), adiponectin (Adipoq), etc. We further evaluated the sensitivity and specificity of MAFB and other clinical parameters for predicting and diagnosing T2DM and found that MAFB expression in PBMCs had a positive effect on the prediction and diagnosis of T2DM. Finally, single-cell RNA sequencing (scRNA-seq) analysis revealed that the increase in MAFB expression was mainly in nonclassical monocytes. Our results suggest that increased MAFB expression in circulating monocytes may mediate chronic inflammatory status in patients with T2DM. Therefore, MAFB gene expression in circulating monocytes has certain clinical significance for predicting and assisting in the diagnosis of T2DM.

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Data Availability

The datasets presented in this study can be found in online repositories. The names of the repositories/repositories and accession numbers can be found in the article/supplementary material.

References

  1. Lee, Y.S., and J. Olefsky. 2021. Chronic tissue inflammation and metabolic disease. Genes & Development 355–6: 307–328.

    Article  Google Scholar 

  2. Zhou, Z., B. Sun, D. Yu, et al. 2022. Gut Microbiota: An important player in type 2 diabetes mellitus. Frontiers in Cellular and Infection Microbiology 12: 834485.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Esser, N., S. Legrand-Poels, J. Piette, et al. 2014. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Research and Clinical Practice 1052: 141–150.

    Article  Google Scholar 

  4. Khodabandehloo, H., S. Gorgani-Firuzjaee, G. Panahi, et al. 2016. Molecular and cellular mechanisms linking inflammation to insulin resistance and beta-cell dysfunction. Translational Research 1671: 228–256.

    Article  Google Scholar 

  5. Thiem, K., S.T. Keating, M.G. Netea, et al. 2021. Hyperglycemic memory of innate immune cells promotes in vitro proinflammatory responses of human monocytes and murine macrophages. The Journal of Immunology 2064: 807–813.

    Article  Google Scholar 

  6. Appari, M., K.M. Channon, and E. McNeill. 2018. Metabolic regulation of adipose tissue macrophage function in obesity and diabetes. Antioxidants & Redox Signaling 293: 297–312.

    Article  Google Scholar 

  7. Boutens, L., and R. Stienstra. 2016. Adipose tissue macrophages: Going off track during obesity. Diabetologia 595: 879–894.

    Article  Google Scholar 

  8. Drareni, K., J.F. Gautier, N. Venteclef, et al. 2019. Transcriptional control of macrophage polarisation in type 2 diabetes. Semin Immunopathol 414: 515–529.

    Article  Google Scholar 

  9. Tesch, G.H. 2007. Role of macrophages in complications of type 2 diabetes. Clinical and Experimental Pharmacology and Physiology 3410: 1016–1019.

    Article  Google Scholar 

  10. O’Grada, C.M., M.J. Morine, C. Morris, et al. 2014. PBMCs reflect the immune component of the WAT transcriptome–implications as biomarkers of metabolic health in the postprandial state. Molecular Nutrition & Food Research 584: 808–820.

    Article  Google Scholar 

  11. Bouwens, M., L.A. Afman, and M. Muller. 2008. Activation of peroxisome proliferator-activated receptor alpha in human peripheral blood mononuclear cells reveals an individual gene expression profile response. BMC Genomics 9: 262.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Gribov, A., M. Sill, S. Luck, et al. 2010. SEURAT: Visual analytics for the integrated analysis of microarray data. BMC Medical Genomics 3: 21.

    Article  PubMed  PubMed Central  Google Scholar 

  13. American Diabetes, A. 2019. Standards of medical care in diabetes-2019 abridged for primary care providers. Clin Diabetes 371: 11–34.

    Article  Google Scholar 

  14. Li, K., Z. Liang, W. Xu, et al. 2022. CTRP7 Is a biomarker related to insulin resistance and oxidative stress: Cross-sectional and intervention studies in vivo and in vitro. Oxidative Medicine and Cellular Longevity 2022: 6877609.

    PubMed  PubMed Central  Google Scholar 

  15. Hu, W., B. Zhan, Q. Li, et al. 2021. Circulating ctrp7 is a potential predictor for metabolic syndrome. Front Endocrinol (Lausanne) 12: 774309.

    Article  PubMed  Google Scholar 

  16. Yang, S., H. Dai, W. Hu, et al. 2021. Association between circulating follistatin-like-1 and metabolic syndrome in middle-aged and old population: A cross-sectional study. Diabetes/Metabolism Research and Reviews 372: e3373.

    Article  Google Scholar 

  17. Albareda, M., J. Rodriguez-Espinosa, M. Murugo, et al. 2000. Assessment of insulin sensitivity and beta-cell function from measurements in the fasting state and during an oral glucose tolerance test. Diabetologia 4312: 1507–1511.

    Article  Google Scholar 

  18. Rao, X., X. Huang, Z. Zhou, et al. 2013. An improvement of the 2^(-delta delta CT) method for quantitative real-time polymerase chain reaction data analysis. Biostatistics, bioinformatics and biomathematics 33: 71–85.

    Google Scholar 

  19. Zhao, A., D. Li, X. Mao, et al. 2022. GNG2 acts as a tumor suppressor in breast cancer through stimulating MRAS signaling. Cell Death & Disease 133: 260.

    Google Scholar 

  20. Hamada, M., Y. Tsunakawa, H. Jeon, et al. 2020. Role of MafB in macrophages. Experimental Animals 691: 1–10.

    Article  Google Scholar 

  21. Guo, S., C. Dai, M. Guo, et al. 2013. Inactivation of specific beta cell transcription factors in type 2 diabetes. The Journal of Clinical Investigation 1238: 3305–3316.

    Article  Google Scholar 

  22. Al Dubayee, M.S., H. Alayed, R. Almansour, et al. 2018. Differential expression of human peripheral mononuclear cells phenotype markers in type 2 diabetic patients and type 2 diabetic patients on metformin. Front Endocrinol (Lausanne) 9: 537.

    Article  PubMed  Google Scholar 

  23. Bleriot, C., E. Dalmas, F. Ginhoux, et al. 2023. Inflammatory and immune etiology of type 2 diabetes. Trends in Immunology 442: 101–109.

    Article  Google Scholar 

  24. Donath, M.Y., and S.E. Shoelson. 2011. Type 2 diabetes as an inflammatory disease. Nature Reviews Immunology 112: 98–107.

    Article  Google Scholar 

  25. Li, H., Y. Meng, S. He, et al. 2022. Macrophages, chronic inflammation, and insulin resistance. Cells 1119

  26. Tran, M.T., M. Hamada, M. Nakamura, et al. 2016. MafB deficiency accelerates the development of obesity in mice. FEBS Open Bio 66: 540–547.

    Article  Google Scholar 

  27. Artner, I., Y. Hang, M. Mazur, et al. 2010. MafA and MafB regulate genes critical to beta-cells in a unique temporal manner. Diabetes 5910: 2530–2539.

    Article  Google Scholar 

  28. Auffray, C., D. Fogg, M. Garfa, et al. 2007. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 3175838: 666–670.

    Article  Google Scholar 

  29. Dick, S.A., J.A. Macklin, S. Nejat, et al. 2019. Self-renewing resident cardiac macrophages limit adverse remodeling following myocardial infarction. Nature Immunology 201: 29–39.

    Article  Google Scholar 

  30. Franklin, R.A., W. Liao, A. Sarkar, et al. 2014. The cellular and molecular origin of tumor-associated macrophages. Science 3446186: 921–925.

    Article  Google Scholar 

  31. Katoh, M.C., Y. Jung, C.M. Ugboma, et al. 2018. MafB is critical for glucagon production and secretion in mouse pancreatic alpha cells in vivoMolecular and cellular biology 388

  32. Tran, M.T.N., M. Hamada, H. Jeon, et al. 2017. MafB is a critical regulator of complement component C1q. Nature Communications 81: 1700.

    Article  Google Scholar 

  33. Su, J.R., Z.H. Lu, Y. Su, et al. 2016. Relationship of serum adiponectin levels and metformin therapy in patients with type 2 diabetes. Hormone and Metabolic Research 482: 92–98.

    Google Scholar 

  34. Huang, T.F., Z.P. Tang, S. Wang, et al. 2019. Decrease in serum levels of adiponectin and increase in 8-OHdG: A culprit for cognitive impairment in the elderly patients with type 2 diabetes. Current Molecular Medicine 201: 44–50.

    Article  Google Scholar 

  35. Engin, A. 2017. Adiponectin-resistance in obesity. Advances in Experimental Medicine and Biology 960: 415–441.

    Article  CAS  PubMed  Google Scholar 

  36. Ouchi, N., J.L. Parker, J.J. Lugus, et al. 2011. Adipokines in inflammation and metabolic disease. Nature Reviews Immunology 112: 85–97.

    Article  Google Scholar 

  37. Sun, L., H. Deng, L. He, et al. 2015. The relationship between NR2E1 and subclinical inflammation in newly diagnosed type 2 diabetic patients. Journal of Diabetes and Its Complications 294: 589–594.

    Article  Google Scholar 

  38. Ratheesh, M., J.P. Svenia, S. Asha, et al. 2017. Anti-inflammatory effect of a novel formulation of coconut inflorescence sap against ox-LDL induced inflammatory responses in human peripheral blood mononuclear cells by modulating TLR-NF-kappaB signaling pathway. Toxicology Mechanisms and Methods 278: 615–621.

    Article  Google Scholar 

  39. Biro, M., M.A. Munoz, and W. Weninger. 2014. Targeting Rho-GTPases in immune cell migration and inflammation. British Journal of Pharmacology 17124: 5491–5506.

    Article  Google Scholar 

  40. Zhou, H., and Y.J. Li. 2010. RhoA/Rho kinase: A novel therapeutic target in diabetic complications. Chinese Medical Journal (Engl) 12317: 2461–2466.

    Google Scholar 

  41. Theocharidis, G., B.E. Thomas, D. Sarkar, et al. 2022. Single cell transcriptomic landscape of diabetic foot ulcers. Nature Communications 131: 181.

    Article  Google Scholar 

  42. Ozanska, A., D. Szymczak, and J. Rybka. 2020. Pattern of human monocyte subpopulations in health and disease. Scandinavian Journal of Immunology 921: e12883.

    Article  Google Scholar 

  43. Zhang, Y., Q. Chen, and A.C. Ross. 2012. Retinoic acid and tumor necrosis factor-alpha induced monocytic cell gene expression is regulated in part by induction of transcription factor MafB. Experimental Cell Research 31818: 2407–2416.

    Article  Google Scholar 

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Acknowledgements

The authors would like to thank all the participants for their participation in this study. We thank the Department of Endocrinology of the Second Affiliated Hospital of Chongqing Medical University for providing professional guidance. The authors thank the professional platform provided by the Key Laboratory of Clinical Laboratory Diagnostics of Ministry of Education, College of Laboratory Medicine, Chongqing Medical University.

Funding

This study was funded by the China Postdoctoral Science Foundation [2022MD713711] and the Chongqing Natural Science Foundation Project—Postdoctoral Science Foundation Project [2022NSCQ-BHX0670].

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Authors and Affiliations

Authors

Contributions

WLZ and WYC made equal contributions to this work. WLZ: Conceptualization, project administration, validation, writing—original draft. WYC: Data curation, supervision, visualization, writing—review and editing. JWL: Formal analysis, validation, writing—review and editing. JL: Data curation, validation, writing—review and editing. MLY: Data curation, formal analysis, methodology, writing—original draft. LL: Conceptualization, funding acquisition, project administration, supervision, writing—review and editing. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Ling Li.

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Ethics Approval

Approval was obtained from the ethics committee of the Second Affiliated Hospital of Chongqing Medical University (Data:12.06.2022 Ratification No. 121/2022). The procedures used in this study were performed in strict adherence to the tenets of the Declaration of Helsinki. Informed consent was obtained from all individual participants included in the study. This animal study was approved by the Institutional Animal Care and Use Committee of Chongqing Medical University (Data: 08.05.2023. Approval No. IACUC-CQMU-2023–06021). The study was conducted in accordance with local legislation and institutional requirements.

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The authors have no competing interests to declare that they are relevant to the content of this article.

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Zhang, W., Chen, W., Lei, J. et al. The Expression of MAFB Gene in Circulating Monocytes Is Related to Chronic Inflammatory Status in T2DM Patients. Inflammation (2024). https://doi.org/10.1007/s10753-024-02012-7

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