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Apelin involved in progression of diabetic nephropathy by inhibiting autophagy in podocytes
Podocyte autophagy dysfunction has been reported to be responsible for the progression of diabetic nephropathy (DN), however, the factors contributed to autophagy dysfunction in type 2 diabetes are not fully understood. Among promoting factors in DN, an adipokine, apelin, had been showed to trigger...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596593/ https://www.ncbi.nlm.nih.gov/pubmed/28837139 http://dx.doi.org/10.1038/cddis.2017.414 |
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author | Liu, Yu Zhang, Jia Wang, Yangjia Zeng, Xiangjun |
author_facet | Liu, Yu Zhang, Jia Wang, Yangjia Zeng, Xiangjun |
author_sort | Liu, Yu |
collection | PubMed |
description | Podocyte autophagy dysfunction has been reported to be responsible for the progression of diabetic nephropathy (DN), however, the factors contributed to autophagy dysfunction in type 2 diabetes are not fully understood. Among promoting factors in DN, an adipokine, apelin, had been showed to trigger podocyte dysfunction. Therefore, it is hypothesized that apelin, which is increased in plasma in type 2 diabetes, lead to podocyte apoptosis through inhibiting podocyte autophagy, which resulted in podocyte dysfunction followed by DN. KkAy mice (diabetic mice) and cultured podocytes (MPC5 cells and native podocytes) were treated with high glucose (HG) and apelin or its antagonist F13A. Renal function, podocyte autophagy, podocyte apoptosis and corresponding cell signaling pathways in podocytes were detected. The results showed that apelin aggravated the renal dysfunction and foot process injuries in kkAy mice, which is positively correlated to podocyte apoptosis and negatively correlated to podocyte autophagy. Apelin induced podocyte apoptosis and inhibited podocyte autophagy in both normal glucose and HG conditions while F13A reversed these effects. Investigations by western blot found that apelin inhibits podocyte autophagy through ERK-, Akt- and mTOR-dependent pathways. In conclusion, increased apelin concentration in plasma inhibited podocyte autophagy, which would lead to podocyte apoptosis and renal dysfunction in diabetes. These effects would contribute to the progression of DN. |
format | Online Article Text |
id | pubmed-5596593 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-55965932017-09-14 Apelin involved in progression of diabetic nephropathy by inhibiting autophagy in podocytes Liu, Yu Zhang, Jia Wang, Yangjia Zeng, Xiangjun Cell Death Dis Original Article Podocyte autophagy dysfunction has been reported to be responsible for the progression of diabetic nephropathy (DN), however, the factors contributed to autophagy dysfunction in type 2 diabetes are not fully understood. Among promoting factors in DN, an adipokine, apelin, had been showed to trigger podocyte dysfunction. Therefore, it is hypothesized that apelin, which is increased in plasma in type 2 diabetes, lead to podocyte apoptosis through inhibiting podocyte autophagy, which resulted in podocyte dysfunction followed by DN. KkAy mice (diabetic mice) and cultured podocytes (MPC5 cells and native podocytes) were treated with high glucose (HG) and apelin or its antagonist F13A. Renal function, podocyte autophagy, podocyte apoptosis and corresponding cell signaling pathways in podocytes were detected. The results showed that apelin aggravated the renal dysfunction and foot process injuries in kkAy mice, which is positively correlated to podocyte apoptosis and negatively correlated to podocyte autophagy. Apelin induced podocyte apoptosis and inhibited podocyte autophagy in both normal glucose and HG conditions while F13A reversed these effects. Investigations by western blot found that apelin inhibits podocyte autophagy through ERK-, Akt- and mTOR-dependent pathways. In conclusion, increased apelin concentration in plasma inhibited podocyte autophagy, which would lead to podocyte apoptosis and renal dysfunction in diabetes. These effects would contribute to the progression of DN. Nature Publishing Group 2017-08 2017-08-24 /pmc/articles/PMC5596593/ /pubmed/28837139 http://dx.doi.org/10.1038/cddis.2017.414 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Liu, Yu Zhang, Jia Wang, Yangjia Zeng, Xiangjun Apelin involved in progression of diabetic nephropathy by inhibiting autophagy in podocytes |
title | Apelin involved in progression of diabetic nephropathy by inhibiting autophagy in podocytes |
title_full | Apelin involved in progression of diabetic nephropathy by inhibiting autophagy in podocytes |
title_fullStr | Apelin involved in progression of diabetic nephropathy by inhibiting autophagy in podocytes |
title_full_unstemmed | Apelin involved in progression of diabetic nephropathy by inhibiting autophagy in podocytes |
title_short | Apelin involved in progression of diabetic nephropathy by inhibiting autophagy in podocytes |
title_sort | apelin involved in progression of diabetic nephropathy by inhibiting autophagy in podocytes |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596593/ https://www.ncbi.nlm.nih.gov/pubmed/28837139 http://dx.doi.org/10.1038/cddis.2017.414 |
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