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DsbA-L Ameliorates Renal Injury Through the AMPK/NLRP3 Inflammasome Signaling Pathway in Diabetic Nephropathy

NLRP3-mediated inflammation is closely related to the pathological progression of diabetic nephropathy (DN). DsbA-L, an antioxidant enzyme, plays a protective role in a variety of diseases by inhibiting ER stress and regulating metabolism. However, the relationship of DsbA-L with inflammation, espec...

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Autores principales: Yang, Ming, Luo, Shilu, Jiang, Na, Wang, Xi, Han, Yachun, Zhao, Hao, Xiong, Xiaofen, Liu, Yan, Zhao, Chanyue, Zhu, Xuejing, Sun, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120163/
https://www.ncbi.nlm.nih.gov/pubmed/33995126
http://dx.doi.org/10.3389/fphys.2021.659751
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author Yang, Ming
Luo, Shilu
Jiang, Na
Wang, Xi
Han, Yachun
Zhao, Hao
Xiong, Xiaofen
Liu, Yan
Zhao, Chanyue
Zhu, Xuejing
Sun, Lin
author_facet Yang, Ming
Luo, Shilu
Jiang, Na
Wang, Xi
Han, Yachun
Zhao, Hao
Xiong, Xiaofen
Liu, Yan
Zhao, Chanyue
Zhu, Xuejing
Sun, Lin
author_sort Yang, Ming
collection PubMed
description NLRP3-mediated inflammation is closely related to the pathological progression of diabetic nephropathy (DN). DsbA-L, an antioxidant enzyme, plays a protective role in a variety of diseases by inhibiting ER stress and regulating metabolism. However, the relationship of DsbA-L with inflammation, especially the NLRP3 inflammasome, has not been examined. In this study, we note that activation of the NLRP3 inflammasome and exacerbated fibrosis were observed in the kidneys of diabetic DsbA-L-knockout mice and were accompanied by decreased phosphorylation of AMP-activated protein kinase (AMPK). Moreover, correlation analysis shows that the phosphorylation of AMPK was negatively correlated with NLRP3 expression and tubular damage. In addition, the decreased AMPK phosphorylation and NLRP3 activation induced by high glucose (HG) in HK-2 cells could be alleviated by the overexpression of DsbA-L. Interestingly, the protective effect of DsbA-L was eliminated after treatment with compound C, a well-known AMPK inhibitor. Our findings suggest that DsbA-L inhibits NLRP3 inflammasome activation by promoting the phosphorylation of AMPK.
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spelling pubmed-81201632021-05-15 DsbA-L Ameliorates Renal Injury Through the AMPK/NLRP3 Inflammasome Signaling Pathway in Diabetic Nephropathy Yang, Ming Luo, Shilu Jiang, Na Wang, Xi Han, Yachun Zhao, Hao Xiong, Xiaofen Liu, Yan Zhao, Chanyue Zhu, Xuejing Sun, Lin Front Physiol Physiology NLRP3-mediated inflammation is closely related to the pathological progression of diabetic nephropathy (DN). DsbA-L, an antioxidant enzyme, plays a protective role in a variety of diseases by inhibiting ER stress and regulating metabolism. However, the relationship of DsbA-L with inflammation, especially the NLRP3 inflammasome, has not been examined. In this study, we note that activation of the NLRP3 inflammasome and exacerbated fibrosis were observed in the kidneys of diabetic DsbA-L-knockout mice and were accompanied by decreased phosphorylation of AMP-activated protein kinase (AMPK). Moreover, correlation analysis shows that the phosphorylation of AMPK was negatively correlated with NLRP3 expression and tubular damage. In addition, the decreased AMPK phosphorylation and NLRP3 activation induced by high glucose (HG) in HK-2 cells could be alleviated by the overexpression of DsbA-L. Interestingly, the protective effect of DsbA-L was eliminated after treatment with compound C, a well-known AMPK inhibitor. Our findings suggest that DsbA-L inhibits NLRP3 inflammasome activation by promoting the phosphorylation of AMPK. Frontiers Media S.A. 2021-04-30 /pmc/articles/PMC8120163/ /pubmed/33995126 http://dx.doi.org/10.3389/fphys.2021.659751 Text en Copyright © 2021 Yang, Luo, Jiang, Wang, Han, Zhao, Xiong, Liu, Zhao, Zhu and Sun. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Yang, Ming
Luo, Shilu
Jiang, Na
Wang, Xi
Han, Yachun
Zhao, Hao
Xiong, Xiaofen
Liu, Yan
Zhao, Chanyue
Zhu, Xuejing
Sun, Lin
DsbA-L Ameliorates Renal Injury Through the AMPK/NLRP3 Inflammasome Signaling Pathway in Diabetic Nephropathy
title DsbA-L Ameliorates Renal Injury Through the AMPK/NLRP3 Inflammasome Signaling Pathway in Diabetic Nephropathy
title_full DsbA-L Ameliorates Renal Injury Through the AMPK/NLRP3 Inflammasome Signaling Pathway in Diabetic Nephropathy
title_fullStr DsbA-L Ameliorates Renal Injury Through the AMPK/NLRP3 Inflammasome Signaling Pathway in Diabetic Nephropathy
title_full_unstemmed DsbA-L Ameliorates Renal Injury Through the AMPK/NLRP3 Inflammasome Signaling Pathway in Diabetic Nephropathy
title_short DsbA-L Ameliorates Renal Injury Through the AMPK/NLRP3 Inflammasome Signaling Pathway in Diabetic Nephropathy
title_sort dsba-l ameliorates renal injury through the ampk/nlrp3 inflammasome signaling pathway in diabetic nephropathy
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120163/
https://www.ncbi.nlm.nih.gov/pubmed/33995126
http://dx.doi.org/10.3389/fphys.2021.659751
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