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A novel function for fibroblast growth factor 21: stimulation of NADPH oxidase-dependent ROS generation

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Abstract

Fibroblast growth factor 21 (FGF-21) is a major paracrine and endocrine regulator of metabolic homeostasis. Here we demonstrate that FGF-21 is also a potent mediator of innate immunity. Double-staining flow cytometry identified neutrophils and monocytes as the main sources of FGF-21 among circulating leukocytes. Functional assays showed that FGF-21 stimulates phagocytosis and production of reactive oxygen species in neutrophil-like HL-60 cells and monocytic THP-1 cells. The mechanism of action of FGF-21 was observed to involve FGF receptor activation, signal transduction through the PI3K/Akt pathway, and stimulation of NADPH oxidase activity. This study indicates that FGF-21 could be an attractive target for the management of inflammatory disorders.

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Acknowledgments

This study was supported by grants from Heilongjiang province project of applied technology research and development (No. GC13C105) and Doctoral scientific research foundation of Northeast Agricultural University project (No. 2010RCB52) and The National Natural Science Fund biologic science base improve program of research training and capacity J1210069/J0131.

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The authors have no conflict of interest to declare for this study.

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Correspondence to Wen-fei Wang or De-shan Li.

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Wen-fei Wang and Lei Ma are co-first authors.

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Wang, Wf., Ma, L., Liu, My. et al. A novel function for fibroblast growth factor 21: stimulation of NADPH oxidase-dependent ROS generation. Endocrine 49, 385–395 (2015). https://doi.org/10.1007/s12020-014-0502-9

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