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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Format: | Article |
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Elsevier
2017-10-01
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Series: | Redox Biology |
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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. |
first_indexed | 2024-12-19T03:48:54Z |
format | Article |
id | doaj.art-deb9cef8872b4e03a03adc572a455d33 |
institution | Directory Open Access Journal |
issn | 2213-2317 |
language | English |
last_indexed | 2024-12-19T03:48:54Z |
publishDate | 2017-10-01 |
publisher | Elsevier |
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series | Redox Biology |
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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