Caveolin 1-related autophagy initiated by aldosterone-induced oxidation promotes liver sinusoidal endothelial cells defenestration

Aldosterone, with pro-oxidation and pro-autophagy capabilities, plays a key role in liver fibrosis. However, the mechanisms underlying aldosterone-promoted liver sinusoidal endothelial cells (LSECs) defenestration remain unknown. Caveolin 1 (Cav1) displays close links with autophagy and fenestration...

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Main Authors: Xiaoying Luo, Dan Wang, Xuan Luo, Xintao Zhu, Guozhen Wang, Zuowei Ning, Yang Li, Xiaoxin Ma, Renqiang Yang, Siyi Jin, Yun Huang, Ying Meng, Xu Li
Format: Article
Language:English
Published: Elsevier 2017-10-01
Series:Redox Biology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2213231717302719
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author Xiaoying Luo
Dan Wang
Xuan Luo
Xintao Zhu
Guozhen Wang
Zuowei Ning
Yang Li
Xiaoxin Ma
Renqiang Yang
Siyi Jin
Yun Huang
Ying Meng
Xu Li
author_facet Xiaoying Luo
Dan Wang
Xuan Luo
Xintao Zhu
Guozhen Wang
Zuowei Ning
Yang Li
Xiaoxin Ma
Renqiang Yang
Siyi Jin
Yun Huang
Ying Meng
Xu Li
author_sort Xiaoying Luo
collection DOAJ
description Aldosterone, with pro-oxidation and pro-autophagy capabilities, plays a key role in liver fibrosis. However, the mechanisms underlying aldosterone-promoted liver sinusoidal endothelial cells (LSECs) defenestration remain unknown. Caveolin 1 (Cav1) displays close links with autophagy and fenestration. Hence, we aim to investigate the role of Cav1-related autophagy in LSECs defenestration. We found the increase of aldosterone/MR (mineralocorticoid receptor) level, oxidation, autophagy, and defenestration in LSECs in the human fibrotic liver, BDL or hyperaldosteronism models; while antagonizing aldosterone or inhibiting autophagy relieved LSECs defenestration in BDL-induced fibrosis or hyperaldosteronism models. In vitro, fenestrae of primary LSECs gradually shrank, along with the down-regulation of the NO-dependent pathway and the augment of the AMPK-dependent autophagy; these effects were aggravated by rapamycin (an autophagy activator) or aldosterone treatment. Additionally, aldosterone increased oxidation mediated by Cav1, reduced ATP generation, and subsequently induced the AMPK-dependent autophagy, leading to the down-regulation of the NO-dependent pathway and LSECs defenestration. These effects were reversed by MR antagonist spironolactone, antioxidants or autophagy inhibitors. Besides, aldosterone enhanced the co-immunoprecipitation of Cav1 with p62 and ubiquitin, and induced Cav1 co-immunofluorescence staining with LC3, ubiquitin, and F-actin in the perinuclear area of LSECs. Furthermore, aldosterone treatment increased the membrane protein level of Cav1, whereas decrease the cytoplasmic protein level of Cav1, indicating that aldosterone induced Cav1-related selective autophagy and F-actin remodeling to promote defenestration. Consequently, Cav1-related selective autophagy initiated by aldosterone-induced oxidation promotes LSECs defenestration via activating the AMPK-ULK1 pathway and inhibiting the NO-dependent pathway.
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spelling doaj.art-deb9cef8872b4e03a03adc572a455d332022-12-21T20:37:03ZengElsevierRedox Biology2213-23172017-10-0113C50852110.1016/j.redox.2017.07.011Caveolin 1-related autophagy initiated by aldosterone-induced oxidation promotes liver sinusoidal endothelial cells defenestrationXiaoying Luo0Dan Wang1Xuan Luo2Xintao Zhu3Guozhen Wang4Zuowei Ning5Yang Li6Xiaoxin Ma7Renqiang Yang8Siyi Jin9Yun Huang10Ying Meng11Xu Li12Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Hepatobiliary Surgery, Guizhou Provincial People's Hospital, No. 52 Zhongshan East Road Nanming District, Guiyang, Guizhou Province, ChinaSouthern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Emergency and Critical Care Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Respiratory Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaAldosterone, with pro-oxidation and pro-autophagy capabilities, plays a key role in liver fibrosis. However, the mechanisms underlying aldosterone-promoted liver sinusoidal endothelial cells (LSECs) defenestration remain unknown. Caveolin 1 (Cav1) displays close links with autophagy and fenestration. Hence, we aim to investigate the role of Cav1-related autophagy in LSECs defenestration. We found the increase of aldosterone/MR (mineralocorticoid receptor) level, oxidation, autophagy, and defenestration in LSECs in the human fibrotic liver, BDL or hyperaldosteronism models; while antagonizing aldosterone or inhibiting autophagy relieved LSECs defenestration in BDL-induced fibrosis or hyperaldosteronism models. In vitro, fenestrae of primary LSECs gradually shrank, along with the down-regulation of the NO-dependent pathway and the augment of the AMPK-dependent autophagy; these effects were aggravated by rapamycin (an autophagy activator) or aldosterone treatment. Additionally, aldosterone increased oxidation mediated by Cav1, reduced ATP generation, and subsequently induced the AMPK-dependent autophagy, leading to the down-regulation of the NO-dependent pathway and LSECs defenestration. These effects were reversed by MR antagonist spironolactone, antioxidants or autophagy inhibitors. Besides, aldosterone enhanced the co-immunoprecipitation of Cav1 with p62 and ubiquitin, and induced Cav1 co-immunofluorescence staining with LC3, ubiquitin, and F-actin in the perinuclear area of LSECs. Furthermore, aldosterone treatment increased the membrane protein level of Cav1, whereas decrease the cytoplasmic protein level of Cav1, indicating that aldosterone induced Cav1-related selective autophagy and F-actin remodeling to promote defenestration. Consequently, Cav1-related selective autophagy initiated by aldosterone-induced oxidation promotes LSECs defenestration via activating the AMPK-ULK1 pathway and inhibiting the NO-dependent pathway.http://www.sciencedirect.com/science/article/pii/S2213231717302719AutophagyLiver sinusoidal endothelial cellDefenestrationAldosteroneCaveolin 1Oxidation
spellingShingle Xiaoying Luo
Dan Wang
Xuan Luo
Xintao Zhu
Guozhen Wang
Zuowei Ning
Yang Li
Xiaoxin Ma
Renqiang Yang
Siyi Jin
Yun Huang
Ying Meng
Xu Li
Caveolin 1-related autophagy initiated by aldosterone-induced oxidation promotes liver sinusoidal endothelial cells defenestration
Redox Biology
Autophagy
Liver sinusoidal endothelial cell
Defenestration
Aldosterone
Caveolin 1
Oxidation
title Caveolin 1-related autophagy initiated by aldosterone-induced oxidation promotes liver sinusoidal endothelial cells defenestration
title_full Caveolin 1-related autophagy initiated by aldosterone-induced oxidation promotes liver sinusoidal endothelial cells defenestration
title_fullStr Caveolin 1-related autophagy initiated by aldosterone-induced oxidation promotes liver sinusoidal endothelial cells defenestration
title_full_unstemmed Caveolin 1-related autophagy initiated by aldosterone-induced oxidation promotes liver sinusoidal endothelial cells defenestration
title_short Caveolin 1-related autophagy initiated by aldosterone-induced oxidation promotes liver sinusoidal endothelial cells defenestration
title_sort caveolin 1 related autophagy initiated by aldosterone induced oxidation promotes liver sinusoidal endothelial cells defenestration
topic Autophagy
Liver sinusoidal endothelial cell
Defenestration
Aldosterone
Caveolin 1
Oxidation
url http://www.sciencedirect.com/science/article/pii/S2213231717302719
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