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IL-37 Ameliorates Renal Fibrosis by Restoring CPT1A-Mediated Fatty Acid Oxidation in Diabetic Kidney Disease
INTRODUCTION: Diabetic kidney disease (DKD) is a major source of chronic kidney disease and end-stage renal disease. The injury of glomerulus in DKD is the primary focus; however, proximal tubulopathy also is an indispensable factor in the progression of DKD. Interleukin-37 (IL-37), an anti-inflamma...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
S. Karger AG
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10090981/ https://www.ncbi.nlm.nih.gov/pubmed/37065609 http://dx.doi.org/10.1159/000529460 |
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author | Xiong, Li He, Ting Liu, Chi Qin, Shaozong Xiao, Tangli Xin, Wang Wang, Yaqin Ran, Li Zhang, Bo Zhao, Jinghong |
author_facet | Xiong, Li He, Ting Liu, Chi Qin, Shaozong Xiao, Tangli Xin, Wang Wang, Yaqin Ran, Li Zhang, Bo Zhao, Jinghong |
author_sort | Xiong, Li |
collection | PubMed |
description | INTRODUCTION: Diabetic kidney disease (DKD) is a major source of chronic kidney disease and end-stage renal disease. The injury of glomerulus in DKD is the primary focus; however, proximal tubulopathy also is an indispensable factor in the progression of DKD. Interleukin-37 (IL-37), an anti-inflammatory cytokine of IL-1 family member, has been demonstrated to be associated with diabetes and its relative complications in recent years, but the effect of IL-37 on renal fibrosis in DKD is unclear. METHODS: We established streptozotocin plus high fat diet-induced DKD mice model with wild type or IL-37 transgenic mice. Masson and HE staining, immunostaining, and Western blot were used to observe renal fibrosis. In addition, RNA-sequencing was applied to explore the potential mechanisms of IL-37. In vitro, treatment of human proximal tubular (HK-2) cells with 30 mmol/L high glucose or 300 ng/mL recombinant IL-37 further elucidated the possible mechanism of IL-37 inhibition of DKD renal fibrosis. RESULTS: In this work, we first verified the decreased expression of IL-37 in kidney of DKD patient and its correlation with clinical features of renal impairment. Moreover, IL-37 expression markedly attenuated proteinuria and renal fibrosis in DKD mice. Using RNA-sequencing, we found and confirmed a novel role of IL-37 in ameliorating fatty acid oxidation (FAO) reduction of renal tubular epithelial cells both in vivo and in intro. In addition, further mechanistic studies showed that IL-37 alleviated the FAO reduction in HK-2 cells and renal fibrosis in DKD mice through upregulating carnitine palmitoyl-transferase 1A (CPT1A), an important catalyzer for FAO pathway. CONCLUSION: These data suggest that IL-37 attenuates renal fibrosis via regulating FAO in renal epithelial cells. Upregulation of IL-37 levels might be an effective therapeutic avenue for DKD. |
format | Online Article Text |
id | pubmed-10090981 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | S. Karger AG |
record_format | MEDLINE/PubMed |
spelling | pubmed-100909812023-04-13 IL-37 Ameliorates Renal Fibrosis by Restoring CPT1A-Mediated Fatty Acid Oxidation in Diabetic Kidney Disease Xiong, Li He, Ting Liu, Chi Qin, Shaozong Xiao, Tangli Xin, Wang Wang, Yaqin Ran, Li Zhang, Bo Zhao, Jinghong Kidney Dis (Basel) Research Article INTRODUCTION: Diabetic kidney disease (DKD) is a major source of chronic kidney disease and end-stage renal disease. The injury of glomerulus in DKD is the primary focus; however, proximal tubulopathy also is an indispensable factor in the progression of DKD. Interleukin-37 (IL-37), an anti-inflammatory cytokine of IL-1 family member, has been demonstrated to be associated with diabetes and its relative complications in recent years, but the effect of IL-37 on renal fibrosis in DKD is unclear. METHODS: We established streptozotocin plus high fat diet-induced DKD mice model with wild type or IL-37 transgenic mice. Masson and HE staining, immunostaining, and Western blot were used to observe renal fibrosis. In addition, RNA-sequencing was applied to explore the potential mechanisms of IL-37. In vitro, treatment of human proximal tubular (HK-2) cells with 30 mmol/L high glucose or 300 ng/mL recombinant IL-37 further elucidated the possible mechanism of IL-37 inhibition of DKD renal fibrosis. RESULTS: In this work, we first verified the decreased expression of IL-37 in kidney of DKD patient and its correlation with clinical features of renal impairment. Moreover, IL-37 expression markedly attenuated proteinuria and renal fibrosis in DKD mice. Using RNA-sequencing, we found and confirmed a novel role of IL-37 in ameliorating fatty acid oxidation (FAO) reduction of renal tubular epithelial cells both in vivo and in intro. In addition, further mechanistic studies showed that IL-37 alleviated the FAO reduction in HK-2 cells and renal fibrosis in DKD mice through upregulating carnitine palmitoyl-transferase 1A (CPT1A), an important catalyzer for FAO pathway. CONCLUSION: These data suggest that IL-37 attenuates renal fibrosis via regulating FAO in renal epithelial cells. Upregulation of IL-37 levels might be an effective therapeutic avenue for DKD. S. Karger AG 2023-01-31 /pmc/articles/PMC10090981/ /pubmed/37065609 http://dx.doi.org/10.1159/000529460 Text en Copyright © 2023 by The Author(s). Published by S. Karger AG, Basel https://creativecommons.org/licenses/by-nc/4.0/This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission. |
spellingShingle | Research Article Xiong, Li He, Ting Liu, Chi Qin, Shaozong Xiao, Tangli Xin, Wang Wang, Yaqin Ran, Li Zhang, Bo Zhao, Jinghong IL-37 Ameliorates Renal Fibrosis by Restoring CPT1A-Mediated Fatty Acid Oxidation in Diabetic Kidney Disease |
title | IL-37 Ameliorates Renal Fibrosis by Restoring CPT1A-Mediated Fatty Acid Oxidation in Diabetic Kidney Disease |
title_full | IL-37 Ameliorates Renal Fibrosis by Restoring CPT1A-Mediated Fatty Acid Oxidation in Diabetic Kidney Disease |
title_fullStr | IL-37 Ameliorates Renal Fibrosis by Restoring CPT1A-Mediated Fatty Acid Oxidation in Diabetic Kidney Disease |
title_full_unstemmed | IL-37 Ameliorates Renal Fibrosis by Restoring CPT1A-Mediated Fatty Acid Oxidation in Diabetic Kidney Disease |
title_short | IL-37 Ameliorates Renal Fibrosis by Restoring CPT1A-Mediated Fatty Acid Oxidation in Diabetic Kidney Disease |
title_sort | il-37 ameliorates renal fibrosis by restoring cpt1a-mediated fatty acid oxidation in diabetic kidney disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10090981/ https://www.ncbi.nlm.nih.gov/pubmed/37065609 http://dx.doi.org/10.1159/000529460 |
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