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Acute glucose fluctuation promotes RAGE expression via reactive oxygen species-mediated NF-κB activation in rat podocytes

Diabetic nephropathy (DN) is a common chronic complication of diabetes, for which acute glucose fluctuation (AGF) is a potential risk factor. Fluctuating hyperglycemia has been confirmed to induce more serious kidney damage than hyperglycemia in diabetic rats; however, the mechanism remains unknown....

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Autores principales: Hu, Zhangjie, Fang, Wenming, Liu, Yi, Liang, Haowei, Chen, Wei, Wang, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974412/
https://www.ncbi.nlm.nih.gov/pubmed/33760170
http://dx.doi.org/10.3892/mmr.2021.11969
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author Hu, Zhangjie
Fang, Wenming
Liu, Yi
Liang, Haowei
Chen, Wei
Wang, Hui
author_facet Hu, Zhangjie
Fang, Wenming
Liu, Yi
Liang, Haowei
Chen, Wei
Wang, Hui
author_sort Hu, Zhangjie
collection PubMed
description Diabetic nephropathy (DN) is a common chronic complication of diabetes, for which acute glucose fluctuation (AGF) is a potential risk factor. Fluctuating hyperglycemia has been confirmed to induce more serious kidney damage than hyperglycemia in diabetic rats; however, the mechanism remains unknown. The purpose of this study was to explore the potential role of AGF in the progression of DN. Viability of rat podocytes following 72-h AGF treatment was detected using Cell Counting-Kit-8. The rates of apoptosis and the level of reactive oxygen species (ROS) in rat podocytes were assessed by flow cytometry. Western blotting and reverse transcription-quantitative PCR were performed to measure relative protein and mRNA expression levels, respectively. Transfection with an mRFP-GFP-LC3 adenoviral vector was used to track autophagic flux under confocal microscopy. The results indicated that AGF could inhibit cell proliferation, promote TNF-α, interleukin-1β (IL-1β), and reactive oxygen species (ROS) generation, and increase autophagy in rat podocytes. Moreover, AGF upregulated receptor for advanced glycation end products (RAGE) expression via activation of NF-κB/p65 and IκBα. Pretreatment with 5 mM N-Acetyl-L-cysteine or 10 µM pyrrolidine dithiocarbamate effectively reduced cellular damage and inhibited activation of the NF-κB/RAGE signaling pathway. Thus, AGF induces rat podocyte injury by aggravating oxidative stress, promoting the inflammatory response, and regulating ROS-mediated NF-κB/RAGE activation.
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spelling pubmed-79744122021-03-24 Acute glucose fluctuation promotes RAGE expression via reactive oxygen species-mediated NF-κB activation in rat podocytes Hu, Zhangjie Fang, Wenming Liu, Yi Liang, Haowei Chen, Wei Wang, Hui Mol Med Rep Articles Diabetic nephropathy (DN) is a common chronic complication of diabetes, for which acute glucose fluctuation (AGF) is a potential risk factor. Fluctuating hyperglycemia has been confirmed to induce more serious kidney damage than hyperglycemia in diabetic rats; however, the mechanism remains unknown. The purpose of this study was to explore the potential role of AGF in the progression of DN. Viability of rat podocytes following 72-h AGF treatment was detected using Cell Counting-Kit-8. The rates of apoptosis and the level of reactive oxygen species (ROS) in rat podocytes were assessed by flow cytometry. Western blotting and reverse transcription-quantitative PCR were performed to measure relative protein and mRNA expression levels, respectively. Transfection with an mRFP-GFP-LC3 adenoviral vector was used to track autophagic flux under confocal microscopy. The results indicated that AGF could inhibit cell proliferation, promote TNF-α, interleukin-1β (IL-1β), and reactive oxygen species (ROS) generation, and increase autophagy in rat podocytes. Moreover, AGF upregulated receptor for advanced glycation end products (RAGE) expression via activation of NF-κB/p65 and IκBα. Pretreatment with 5 mM N-Acetyl-L-cysteine or 10 µM pyrrolidine dithiocarbamate effectively reduced cellular damage and inhibited activation of the NF-κB/RAGE signaling pathway. Thus, AGF induces rat podocyte injury by aggravating oxidative stress, promoting the inflammatory response, and regulating ROS-mediated NF-κB/RAGE activation. D.A. Spandidos 2021-05 2021-03-08 /pmc/articles/PMC7974412/ /pubmed/33760170 http://dx.doi.org/10.3892/mmr.2021.11969 Text en Copyright: © Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Hu, Zhangjie
Fang, Wenming
Liu, Yi
Liang, Haowei
Chen, Wei
Wang, Hui
Acute glucose fluctuation promotes RAGE expression via reactive oxygen species-mediated NF-κB activation in rat podocytes
title Acute glucose fluctuation promotes RAGE expression via reactive oxygen species-mediated NF-κB activation in rat podocytes
title_full Acute glucose fluctuation promotes RAGE expression via reactive oxygen species-mediated NF-κB activation in rat podocytes
title_fullStr Acute glucose fluctuation promotes RAGE expression via reactive oxygen species-mediated NF-κB activation in rat podocytes
title_full_unstemmed Acute glucose fluctuation promotes RAGE expression via reactive oxygen species-mediated NF-κB activation in rat podocytes
title_short Acute glucose fluctuation promotes RAGE expression via reactive oxygen species-mediated NF-κB activation in rat podocytes
title_sort acute glucose fluctuation promotes rage expression via reactive oxygen species-mediated nf-κb activation in rat podocytes
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974412/
https://www.ncbi.nlm.nih.gov/pubmed/33760170
http://dx.doi.org/10.3892/mmr.2021.11969
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