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ELABELA protects against diabetic kidney disease by activating high glucose-inhibited renal tubular autophagy
ELABELA (ELA), an endogenous ligand of the apelin receptor (also known as apelin peptide jejunum [APJ]), has been shown to decrease in the plasma of patients with diabetic kidney disease (DKD). In the current study, we explored the potential function as well as the underlying mechanisms of ELA in DK...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Editorial Department of Journal of Biomedical Research
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687528/ https://www.ncbi.nlm.nih.gov/pubmed/38018421 http://dx.doi.org/10.7555/JBR.37.20220214 |
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author | Zheng, Xiyin Yin, Lulu Song, Jing Chen, Juan Gu, Wensha Shi, Min Zhang, Hong |
author_facet | Zheng, Xiyin Yin, Lulu Song, Jing Chen, Juan Gu, Wensha Shi, Min Zhang, Hong |
author_sort | Zheng, Xiyin |
collection | PubMed |
description | ELABELA (ELA), an endogenous ligand of the apelin receptor (also known as apelin peptide jejunum [APJ]), has been shown to decrease in the plasma of patients with diabetic kidney disease (DKD). In the current study, we explored the potential function as well as the underlying mechanisms of ELA in DKD. We first found that the ELA levels were decreased in the kidneys of DKD mice. Then, we found that ELA administration mitigated renal damage and downregulated the expression of fibronectin, collagen Ⅳ, and transforming growth factor-β1 in the db/db mice and the high glucose cultured HK-2 cells. Furthermore, the autophagy markers, Beclin-1 and LC3-Ⅱ/LC3-Ⅰ ratio, were significantly impaired in DKD, but the ELA treatment reversed these alterations. Mechanistically, the inhibitory effects of ELA on the secretion of fibrosis-associated proteins in high glucose conditions were blocked by pretreatment with 3-methyladenine (an autophagy inhibitor). In summary, these in vivo and in vitro results demonstrate that ELA effectively protects against DKD by activating high glucose-inhibited renal tubular autophagy, potentially serving as a novel therapeutic candidate for DKD. |
format | Online Article Text |
id | pubmed-10687528 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Editorial Department of Journal of Biomedical Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-106875282023-12-01 ELABELA protects against diabetic kidney disease by activating high glucose-inhibited renal tubular autophagy Zheng, Xiyin Yin, Lulu Song, Jing Chen, Juan Gu, Wensha Shi, Min Zhang, Hong J Biomed Res Original Article ELABELA (ELA), an endogenous ligand of the apelin receptor (also known as apelin peptide jejunum [APJ]), has been shown to decrease in the plasma of patients with diabetic kidney disease (DKD). In the current study, we explored the potential function as well as the underlying mechanisms of ELA in DKD. We first found that the ELA levels were decreased in the kidneys of DKD mice. Then, we found that ELA administration mitigated renal damage and downregulated the expression of fibronectin, collagen Ⅳ, and transforming growth factor-β1 in the db/db mice and the high glucose cultured HK-2 cells. Furthermore, the autophagy markers, Beclin-1 and LC3-Ⅱ/LC3-Ⅰ ratio, were significantly impaired in DKD, but the ELA treatment reversed these alterations. Mechanistically, the inhibitory effects of ELA on the secretion of fibrosis-associated proteins in high glucose conditions were blocked by pretreatment with 3-methyladenine (an autophagy inhibitor). In summary, these in vivo and in vitro results demonstrate that ELA effectively protects against DKD by activating high glucose-inhibited renal tubular autophagy, potentially serving as a novel therapeutic candidate for DKD. Editorial Department of Journal of Biomedical Research 2023-11 2023-11-15 /pmc/articles/PMC10687528/ /pubmed/38018421 http://dx.doi.org/10.7555/JBR.37.20220214 Text en © 2023 by the Journal of Biomedical Research. https://creativecommons.org/licenses/by/4.0/This is an open access article under the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. |
spellingShingle | Original Article Zheng, Xiyin Yin, Lulu Song, Jing Chen, Juan Gu, Wensha Shi, Min Zhang, Hong ELABELA protects against diabetic kidney disease by activating high glucose-inhibited renal tubular autophagy |
title | ELABELA protects against diabetic kidney disease by activating high glucose-inhibited renal tubular autophagy |
title_full | ELABELA protects against diabetic kidney disease by activating high glucose-inhibited renal tubular autophagy |
title_fullStr | ELABELA protects against diabetic kidney disease by activating high glucose-inhibited renal tubular autophagy |
title_full_unstemmed | ELABELA protects against diabetic kidney disease by activating high glucose-inhibited renal tubular autophagy |
title_short | ELABELA protects against diabetic kidney disease by activating high glucose-inhibited renal tubular autophagy |
title_sort | elabela protects against diabetic kidney disease by activating high glucose-inhibited renal tubular autophagy |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687528/ https://www.ncbi.nlm.nih.gov/pubmed/38018421 http://dx.doi.org/10.7555/JBR.37.20220214 |
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