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DOI: 10.1055/s-0041-1726346
Methylglyoxal Drives a Distinct, Nonclassical Macrophage Activation Status
Funding This work was supported by the Collaborative Research Center 1118 “Reactive metabolites and diabetic complications” awarded to P.N. and S.H, the Helmholtz Future Topic AMPro to S.H., and by the Deutsche Forschungsgemeinschaft Sonderforschungsbereich 1123 (B10) as well as the Deutsches Zentrum für Herz-Kreislauf-Forschung Junior Research Group Grant awarded to A.B.Abstract
Metabolic complications in diabetic patients are driven by a combination of increased levels of nutrients and the presence of a proinflammatory environment. Methylglyoxal (MG) is a toxic byproduct of catabolism and has been strongly associated with the development of such complications. Macrophages are key mediators of inflammatory processes and their contribution to the development of metabolic complications has been demonstrated. However, a direct link between reactive metabolites and macrophage activation has not been demonstrated yet. Here, we show that acute MG treatment activated components of the p38 MAPK pathway and enhanced glycolysis in primary murine macrophages. MG induced a distinct gene expression profile sharing similarities with classically activated proinflammatory macrophages as well as metabolically activated macrophages usually found in obese patients. Transcriptomic analysis revealed a set of 15 surface markers specifically upregulated in MG-treated macrophages, thereby establishing a new set of targets for diagnostic or therapeutic purposes under high MG conditions, including diabetes. Overall, our study defines a new polarization state of macrophages that may specifically link aberrant macrophage activation to reactive metabolites in diabetes.
Author Contributions
F-F.T., C.M., and D.H. performed the majority of experiments. S.K. analysed the RNA-Seq data. T.F. performed the quantification of Methylglyoxal. G.W., A.B., and P.N. contributed with experimental advice and discussion of the data. F-F.T., CM., and S.H. conceptually designed the study and analysed the data. F.T., C.M., and S.H. wrote the manuscript.
* F.F.T. and C.M. contributed equally and share the first authorship position.
** S.K. and D.H. share the second authorship position.
Publikationsverlauf
Eingereicht: 04. November 2020
Angenommen: 09. Februar 2021
Artikel online veröffentlicht:
09. Mai 2021
© 2021. Thieme. All rights reserved.
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