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Maresin 1 Alleviates Diabetic Kidney Disease via LGR6-Mediated cAMP-SOD2-ROS Pathway

Background. Chronic hyperglycemia-induced inflammation is recognized as the most important pathophysiological process in diabetic kidney disease (DKD). As maresin 1 (MaR1) is an extensive anti-inflammatory lipid mediator, the present study investigated the protective role of MaR1 in the pathogenesis...

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Autores principales: Li, Xinyue, Xu, Butuo, Wu, Jing, Pu, Yueli, Wan, Shengrong, Zeng, Yan, Wang, Mei, Luo, Lifang, Zhang, Fanjie, Jiang, Zongzhe, Xu, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9042615/
https://www.ncbi.nlm.nih.gov/pubmed/35498124
http://dx.doi.org/10.1155/2022/7177889
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author Li, Xinyue
Xu, Butuo
Wu, Jing
Pu, Yueli
Wan, Shengrong
Zeng, Yan
Wang, Mei
Luo, Lifang
Zhang, Fanjie
Jiang, Zongzhe
Xu, Yong
author_facet Li, Xinyue
Xu, Butuo
Wu, Jing
Pu, Yueli
Wan, Shengrong
Zeng, Yan
Wang, Mei
Luo, Lifang
Zhang, Fanjie
Jiang, Zongzhe
Xu, Yong
author_sort Li, Xinyue
collection PubMed
description Background. Chronic hyperglycemia-induced inflammation is recognized as the most important pathophysiological process in diabetic kidney disease (DKD). As maresin 1 (MaR1) is an extensive anti-inflammatory lipid mediator, the present study investigated the protective role of MaR1 in the pathogenesis of DKD and its clinical relevance. Methods. Serum MaR1 concentrations were analyzed in 104 subjects with normal glucose tolerant, type 2 diabetes (T2DM), or DKD. Streptozotocin (STZ) together with high fat diet was used to induce male C57BL/6 J mice into diabetic mice which were treated with MaR1. Human renal tubule epithelial cells (HK-2 cells) were treated by high glucose for glucotoxicity cell model and transfected with LGR6 siRNA for knockdown with MaR1 added,and detected oxidative stress and inflammatory related factors. Results. Serum MaR1 concentrations were significant decreased in T2DM with or without kidney disease compared with normal participant and were lowest in patients with DKD. Serum MaR1 concentrations were negatively correlated with hemoglobin A1c (HbA1c), duration of diabetes, urinary albumin to creatinine ratio (UACR), neutrophil, and neutrophil-lymphocyte ratio and were positively correlated with high-density lipoprotein-cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR). In mouse model, MaR1 injection alleviated hyperglycemia, UACR and the pathological progression of DKD. Interestingly, the renal expression of LGR6 was down-regulated in DKD and high glucose treated HK-2 cells but up-regulated by MaR1 treatment. Mechanistically, MaR1 alleviated inflammation via LGR6-mediated cAMP-SOD2 antioxidant pathway in DKD mice and high glucose treated HK-2 cells. Conclusions. Our study demonstrates that decreased serum MaR1 levels were correlated with the development of DKD. MaR1 could alleviate DKD and glucotoxicity-induced inflammation via LGR6-mediated cAMP-SOD2 antioxidant pathway. Thus, our present findings identify MaR1 as a predictor and a potential therapeutic target for DKD.
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spelling pubmed-90426152022-04-27 Maresin 1 Alleviates Diabetic Kidney Disease via LGR6-Mediated cAMP-SOD2-ROS Pathway Li, Xinyue Xu, Butuo Wu, Jing Pu, Yueli Wan, Shengrong Zeng, Yan Wang, Mei Luo, Lifang Zhang, Fanjie Jiang, Zongzhe Xu, Yong Oxid Med Cell Longev Research Article Background. Chronic hyperglycemia-induced inflammation is recognized as the most important pathophysiological process in diabetic kidney disease (DKD). As maresin 1 (MaR1) is an extensive anti-inflammatory lipid mediator, the present study investigated the protective role of MaR1 in the pathogenesis of DKD and its clinical relevance. Methods. Serum MaR1 concentrations were analyzed in 104 subjects with normal glucose tolerant, type 2 diabetes (T2DM), or DKD. Streptozotocin (STZ) together with high fat diet was used to induce male C57BL/6 J mice into diabetic mice which were treated with MaR1. Human renal tubule epithelial cells (HK-2 cells) were treated by high glucose for glucotoxicity cell model and transfected with LGR6 siRNA for knockdown with MaR1 added,and detected oxidative stress and inflammatory related factors. Results. Serum MaR1 concentrations were significant decreased in T2DM with or without kidney disease compared with normal participant and were lowest in patients with DKD. Serum MaR1 concentrations were negatively correlated with hemoglobin A1c (HbA1c), duration of diabetes, urinary albumin to creatinine ratio (UACR), neutrophil, and neutrophil-lymphocyte ratio and were positively correlated with high-density lipoprotein-cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR). In mouse model, MaR1 injection alleviated hyperglycemia, UACR and the pathological progression of DKD. Interestingly, the renal expression of LGR6 was down-regulated in DKD and high glucose treated HK-2 cells but up-regulated by MaR1 treatment. Mechanistically, MaR1 alleviated inflammation via LGR6-mediated cAMP-SOD2 antioxidant pathway in DKD mice and high glucose treated HK-2 cells. Conclusions. Our study demonstrates that decreased serum MaR1 levels were correlated with the development of DKD. MaR1 could alleviate DKD and glucotoxicity-induced inflammation via LGR6-mediated cAMP-SOD2 antioxidant pathway. Thus, our present findings identify MaR1 as a predictor and a potential therapeutic target for DKD. Hindawi 2022-04-19 /pmc/articles/PMC9042615/ /pubmed/35498124 http://dx.doi.org/10.1155/2022/7177889 Text en Copyright © 2022 Xinyue Li et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Li, Xinyue
Xu, Butuo
Wu, Jing
Pu, Yueli
Wan, Shengrong
Zeng, Yan
Wang, Mei
Luo, Lifang
Zhang, Fanjie
Jiang, Zongzhe
Xu, Yong
Maresin 1 Alleviates Diabetic Kidney Disease via LGR6-Mediated cAMP-SOD2-ROS Pathway
title Maresin 1 Alleviates Diabetic Kidney Disease via LGR6-Mediated cAMP-SOD2-ROS Pathway
title_full Maresin 1 Alleviates Diabetic Kidney Disease via LGR6-Mediated cAMP-SOD2-ROS Pathway
title_fullStr Maresin 1 Alleviates Diabetic Kidney Disease via LGR6-Mediated cAMP-SOD2-ROS Pathway
title_full_unstemmed Maresin 1 Alleviates Diabetic Kidney Disease via LGR6-Mediated cAMP-SOD2-ROS Pathway
title_short Maresin 1 Alleviates Diabetic Kidney Disease via LGR6-Mediated cAMP-SOD2-ROS Pathway
title_sort maresin 1 alleviates diabetic kidney disease via lgr6-mediated camp-sod2-ros pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9042615/
https://www.ncbi.nlm.nih.gov/pubmed/35498124
http://dx.doi.org/10.1155/2022/7177889
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