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Tubular Mas receptor mediates lipid-induced kidney injury
Obesity-related kidney diseases are becoming serious health problems worldwide, yet the mechanism by which obesity causes kidney injury is not fully understood. The purpose of current study was to investigate the role of Mas receptor in lipid-induced kidney injury. In mice fed with high-fat diet (HF...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817966/ https://www.ncbi.nlm.nih.gov/pubmed/33479200 http://dx.doi.org/10.1038/s41419-020-03375-z |
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author | Kong, Yonglun Zhao, Xiaoduo Qiu, Miaojuan Lin, Yu Feng, Pinning Li, Suchun Liang, Baien Zhu, Qing Huang, Hui Li, Chunling Wang, Weidong |
author_facet | Kong, Yonglun Zhao, Xiaoduo Qiu, Miaojuan Lin, Yu Feng, Pinning Li, Suchun Liang, Baien Zhu, Qing Huang, Hui Li, Chunling Wang, Weidong |
author_sort | Kong, Yonglun |
collection | PubMed |
description | Obesity-related kidney diseases are becoming serious health problems worldwide, yet the mechanism by which obesity causes kidney injury is not fully understood. The purpose of current study was to investigate the role of Mas receptor in lipid-induced kidney injury. In mice fed with high-fat diet (HFD), the protein abundance of markers of autophagy, endoplasmic reticulum stress (ER stress) and apoptosis was dramatically increased in the kidney cortex, which was markedly prevented by Mas deletion (Mas(−/−)) or Mas receptor antagonist A779. Palmitic acid (PA) induced persistently increased autophagy, ER stress, and apoptosis as well as mitochondrial injuries in primary cultured proximal tubular cells from wild type, but not from Mas(−/−) mice. In human proximal tubular HK2 cells, PA-induced autophagy and ER stress was aggravated by Mas agonists Ang (1–7) or AVE0991, but attenuated by A779 or Mas knockdown. Stimulation of Mas resulted in elevated intracellular calcium levels [Ca(2+)](i) in HK2 cells treated with PA, whereas inhibition or knockdown of Mas decreased [Ca(2+)](i). Mitochondrial outer membrane located voltage-dependent anion channel (VDAC1) was markedly upregulated in HK2 cells treated with PA, which was associated with impaired mitochondrial morphology and depolarization. These were enhanced by AVE0991 and suppressed by A779 or Mas knockdown. Mas knockdown in HK2 cells prevented impaired interactions among VDAC1, autophagy adaptor P62, and ubiquitin, induced by PA, leading to a potential ubiquitination of VDAC1. In conclusion, Mas receptor-mediated lipid-induced impaired autophagy and ER stress in the kidney, likely contributing to tubular injuries in obesity-related kidney diseases. |
format | Online Article Text |
id | pubmed-7817966 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78179662021-01-21 Tubular Mas receptor mediates lipid-induced kidney injury Kong, Yonglun Zhao, Xiaoduo Qiu, Miaojuan Lin, Yu Feng, Pinning Li, Suchun Liang, Baien Zhu, Qing Huang, Hui Li, Chunling Wang, Weidong Cell Death Dis Article Obesity-related kidney diseases are becoming serious health problems worldwide, yet the mechanism by which obesity causes kidney injury is not fully understood. The purpose of current study was to investigate the role of Mas receptor in lipid-induced kidney injury. In mice fed with high-fat diet (HFD), the protein abundance of markers of autophagy, endoplasmic reticulum stress (ER stress) and apoptosis was dramatically increased in the kidney cortex, which was markedly prevented by Mas deletion (Mas(−/−)) or Mas receptor antagonist A779. Palmitic acid (PA) induced persistently increased autophagy, ER stress, and apoptosis as well as mitochondrial injuries in primary cultured proximal tubular cells from wild type, but not from Mas(−/−) mice. In human proximal tubular HK2 cells, PA-induced autophagy and ER stress was aggravated by Mas agonists Ang (1–7) or AVE0991, but attenuated by A779 or Mas knockdown. Stimulation of Mas resulted in elevated intracellular calcium levels [Ca(2+)](i) in HK2 cells treated with PA, whereas inhibition or knockdown of Mas decreased [Ca(2+)](i). Mitochondrial outer membrane located voltage-dependent anion channel (VDAC1) was markedly upregulated in HK2 cells treated with PA, which was associated with impaired mitochondrial morphology and depolarization. These were enhanced by AVE0991 and suppressed by A779 or Mas knockdown. Mas knockdown in HK2 cells prevented impaired interactions among VDAC1, autophagy adaptor P62, and ubiquitin, induced by PA, leading to a potential ubiquitination of VDAC1. In conclusion, Mas receptor-mediated lipid-induced impaired autophagy and ER stress in the kidney, likely contributing to tubular injuries in obesity-related kidney diseases. Nature Publishing Group UK 2021-01-21 /pmc/articles/PMC7817966/ /pubmed/33479200 http://dx.doi.org/10.1038/s41419-020-03375-z Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Kong, Yonglun Zhao, Xiaoduo Qiu, Miaojuan Lin, Yu Feng, Pinning Li, Suchun Liang, Baien Zhu, Qing Huang, Hui Li, Chunling Wang, Weidong Tubular Mas receptor mediates lipid-induced kidney injury |
title | Tubular Mas receptor mediates lipid-induced kidney injury |
title_full | Tubular Mas receptor mediates lipid-induced kidney injury |
title_fullStr | Tubular Mas receptor mediates lipid-induced kidney injury |
title_full_unstemmed | Tubular Mas receptor mediates lipid-induced kidney injury |
title_short | Tubular Mas receptor mediates lipid-induced kidney injury |
title_sort | tubular mas receptor mediates lipid-induced kidney injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817966/ https://www.ncbi.nlm.nih.gov/pubmed/33479200 http://dx.doi.org/10.1038/s41419-020-03375-z |
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