TNF induces glycolytic shift in fibroblast like synoviocytes via GLUT1 and HIF1A

Abstract TNF is a central cytokine in the pathogenesis of rheumatoid arthritis (RA). Elevated level of TNF causes local inflammation that affects immune cells and fibroblast-like synoviocytes (FLS). Nowadays, only 20–30% of patients experience remission after the standard of care therapy—antibodies...

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Autores principales:	Kathrin Koedderitzsch, Ekaterina Zezina, Lingzi Li, Matthias Herrmann, Nadine Biesemann
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/695dcc322f0344b397d04593c01b217c
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spelling	oai:doaj.org-article:695dcc322f0344b397d04593c01b217c2021-12-02T18:51:35ZTNF induces glycolytic shift in fibroblast like synoviocytes via GLUT1 and HIF1A10.1038/s41598-021-98651-z2045-2322https://doaj.org/article/695dcc322f0344b397d04593c01b217c2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98651-zhttps://doaj.org/toc/2045-2322Abstract TNF is a central cytokine in the pathogenesis of rheumatoid arthritis (RA). Elevated level of TNF causes local inflammation that affects immune cells and fibroblast-like synoviocytes (FLS). Nowadays, only 20–30% of patients experience remission after the standard of care therapy—antibodies against TNF. Interestingly, responders show reduced levels of GLUT1 and GAPDH, highlighting a potential link to cellular metabolism. The aim of the study was to investigate whether TNF directly affects the metabolic phenotype of FLS. Real-time respirometry displayed TNF-induced upregulation of glycolysis along with a modest increase of oxidative phosphorylation in FLS from healthy donors. In addition, TNF stimulation enhanced HIF1A and GLUT1 expression. The upregulation of HIF1A and GLUT1 reflects their enriched level in FLS from RA patients (RA-FLS). The inhibition of TAK1, HIF1a and hexokinase deciphered the importance of TNF/TAK1/HIF1A/glycolysis signaling axis. To prove that inhibition of glycolysis reduced the pathogenic phenotype, we showed that 2-deoxyglucose, a hexokinase inhibitor, partially decreased secretion of RA biomarkers. In summary, we identified a direct role of TNF on glycolytic reprogramming of FLS and confirmed the potency of immunometabolism for RA. Further studies are needed to evaluate the therapeutic impact especially regarding non-responder data.Kathrin KoedderitzschEkaterina ZezinaLingzi LiMatthias HerrmannNadine BiesemannNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kathrin Koedderitzsch Ekaterina Zezina Lingzi Li Matthias Herrmann Nadine Biesemann TNF induces glycolytic shift in fibroblast like synoviocytes via GLUT1 and HIF1A
description	Abstract TNF is a central cytokine in the pathogenesis of rheumatoid arthritis (RA). Elevated level of TNF causes local inflammation that affects immune cells and fibroblast-like synoviocytes (FLS). Nowadays, only 20–30% of patients experience remission after the standard of care therapy—antibodies against TNF. Interestingly, responders show reduced levels of GLUT1 and GAPDH, highlighting a potential link to cellular metabolism. The aim of the study was to investigate whether TNF directly affects the metabolic phenotype of FLS. Real-time respirometry displayed TNF-induced upregulation of glycolysis along with a modest increase of oxidative phosphorylation in FLS from healthy donors. In addition, TNF stimulation enhanced HIF1A and GLUT1 expression. The upregulation of HIF1A and GLUT1 reflects their enriched level in FLS from RA patients (RA-FLS). The inhibition of TAK1, HIF1a and hexokinase deciphered the importance of TNF/TAK1/HIF1A/glycolysis signaling axis. To prove that inhibition of glycolysis reduced the pathogenic phenotype, we showed that 2-deoxyglucose, a hexokinase inhibitor, partially decreased secretion of RA biomarkers. In summary, we identified a direct role of TNF on glycolytic reprogramming of FLS and confirmed the potency of immunometabolism for RA. Further studies are needed to evaluate the therapeutic impact especially regarding non-responder data.
format	article
author	Kathrin Koedderitzsch Ekaterina Zezina Lingzi Li Matthias Herrmann Nadine Biesemann
author_facet	Kathrin Koedderitzsch Ekaterina Zezina Lingzi Li Matthias Herrmann Nadine Biesemann
author_sort	Kathrin Koedderitzsch
title	TNF induces glycolytic shift in fibroblast like synoviocytes via GLUT1 and HIF1A
title_short	TNF induces glycolytic shift in fibroblast like synoviocytes via GLUT1 and HIF1A
title_full	TNF induces glycolytic shift in fibroblast like synoviocytes via GLUT1 and HIF1A
title_fullStr	TNF induces glycolytic shift in fibroblast like synoviocytes via GLUT1 and HIF1A
title_full_unstemmed	TNF induces glycolytic shift in fibroblast like synoviocytes via GLUT1 and HIF1A
title_sort	tnf induces glycolytic shift in fibroblast like synoviocytes via glut1 and hif1a
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/695dcc322f0344b397d04593c01b217c
work_keys_str_mv	AT kathrinkoedderitzsch tnfinducesglycolyticshiftinfibroblastlikesynoviocytesviaglut1andhif1a AT ekaterinazezina tnfinducesglycolyticshiftinfibroblastlikesynoviocytesviaglut1andhif1a AT lingzili tnfinducesglycolyticshiftinfibroblastlikesynoviocytesviaglut1andhif1a AT matthiasherrmann tnfinducesglycolyticshiftinfibroblastlikesynoviocytesviaglut1andhif1a AT nadinebiesemann tnfinducesglycolyticshiftinfibroblastlikesynoviocytesviaglut1andhif1a
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TNF induces glycolytic shift in fibroblast like synoviocytes via GLUT1 and HIF1A

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