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TAB1 regulates glycolysis and activation of macrophages in diabetic nephropathy

OBJECTIVE AND DESIGN: Macrophages exhibit strong phenotypic plasticity and can mediate renal inflammation by polarizing into an M1 phenotype. They play a pivotal role in diabetic nephropathy (DN). Here, we have investigated the regulatory role of transforming growth factor β-activated kinase 1-bindi...

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Autores principales: Zeng, Hanxu, Qi, Xiangming, Xu, Xingxin, Wu, Yonggui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658079/
https://www.ncbi.nlm.nih.gov/pubmed/33044562
http://dx.doi.org/10.1007/s00011-020-01411-4
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author Zeng, Hanxu
Qi, Xiangming
Xu, Xingxin
Wu, Yonggui
author_facet Zeng, Hanxu
Qi, Xiangming
Xu, Xingxin
Wu, Yonggui
author_sort Zeng, Hanxu
collection PubMed
description OBJECTIVE AND DESIGN: Macrophages exhibit strong phenotypic plasticity and can mediate renal inflammation by polarizing into an M1 phenotype. They play a pivotal role in diabetic nephropathy (DN). Here, we have investigated the regulatory role of transforming growth factor β-activated kinase 1-binding protein 1 (TAB1) in glycolysis and activation of macrophages during DN. METHODS: TAB1 was inhibited using siRNA in high glucose (HG)-stimulated bone marrow-derived macrophages (BMMs) and lentiviral vector-mediated TAB1 knockdown was used in streptozotocin (STZ)-induced diabetic mice. Western blotting, flow cytometry, qRT-PCR, ELISA, PAS staining and immunohistochemical staining were used for assessment of TAB1/nuclear factor-κB (NF-κB)/hypoxia-inducible factor-1α (HIF-1α), iNOS, glycolysis, inflammation and the clinical and pathological manifestations of diabetic nephropathy. RESULTS: We found that TAB1/NF-κB/HIF-1α, iNOS and glycolysis were up-regulated in BMMs under HG conditions, leading to release of further inflammatory factors, Downregulation of TAB1 could inhibit glycolysis/polarization of macrophages and inflammation in vivo and in vitro. Furthermore, albuminuria, the tubulointerstitial damage index and glomerular mesangial expansion index of STZ-induced diabetic nephropathy mice were decreased by TAB1 knockdown. CONCLUSIONS: Our results suggest that the TAB1/NF-κB/HIF-1α signaling pathway regulates glycolysis and activation of macrophages in DN. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00011-020-01411-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-76580792020-11-12 TAB1 regulates glycolysis and activation of macrophages in diabetic nephropathy Zeng, Hanxu Qi, Xiangming Xu, Xingxin Wu, Yonggui Inflamm Res Original Research Paper OBJECTIVE AND DESIGN: Macrophages exhibit strong phenotypic plasticity and can mediate renal inflammation by polarizing into an M1 phenotype. They play a pivotal role in diabetic nephropathy (DN). Here, we have investigated the regulatory role of transforming growth factor β-activated kinase 1-binding protein 1 (TAB1) in glycolysis and activation of macrophages during DN. METHODS: TAB1 was inhibited using siRNA in high glucose (HG)-stimulated bone marrow-derived macrophages (BMMs) and lentiviral vector-mediated TAB1 knockdown was used in streptozotocin (STZ)-induced diabetic mice. Western blotting, flow cytometry, qRT-PCR, ELISA, PAS staining and immunohistochemical staining were used for assessment of TAB1/nuclear factor-κB (NF-κB)/hypoxia-inducible factor-1α (HIF-1α), iNOS, glycolysis, inflammation and the clinical and pathological manifestations of diabetic nephropathy. RESULTS: We found that TAB1/NF-κB/HIF-1α, iNOS and glycolysis were up-regulated in BMMs under HG conditions, leading to release of further inflammatory factors, Downregulation of TAB1 could inhibit glycolysis/polarization of macrophages and inflammation in vivo and in vitro. Furthermore, albuminuria, the tubulointerstitial damage index and glomerular mesangial expansion index of STZ-induced diabetic nephropathy mice were decreased by TAB1 knockdown. CONCLUSIONS: Our results suggest that the TAB1/NF-κB/HIF-1α signaling pathway regulates glycolysis and activation of macrophages in DN. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00011-020-01411-4) contains supplementary material, which is available to authorized users. Springer International Publishing 2020-10-12 2020 /pmc/articles/PMC7658079/ /pubmed/33044562 http://dx.doi.org/10.1007/s00011-020-01411-4 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Original Research Paper
Zeng, Hanxu
Qi, Xiangming
Xu, Xingxin
Wu, Yonggui
TAB1 regulates glycolysis and activation of macrophages in diabetic nephropathy
title TAB1 regulates glycolysis and activation of macrophages in diabetic nephropathy
title_full TAB1 regulates glycolysis and activation of macrophages in diabetic nephropathy
title_fullStr TAB1 regulates glycolysis and activation of macrophages in diabetic nephropathy
title_full_unstemmed TAB1 regulates glycolysis and activation of macrophages in diabetic nephropathy
title_short TAB1 regulates glycolysis and activation of macrophages in diabetic nephropathy
title_sort tab1 regulates glycolysis and activation of macrophages in diabetic nephropathy
topic Original Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658079/
https://www.ncbi.nlm.nih.gov/pubmed/33044562
http://dx.doi.org/10.1007/s00011-020-01411-4
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AT wuyonggui tab1regulatesglycolysisandactivationofmacrophagesindiabeticnephropathy