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Tytuł:
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ROS/p38MAPK-induced lamin B1 accumulation promotes chronic kidney disease-associated vascular smooth muscle cells senescence.
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Autorzy:
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Wang X; Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), China; Laboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University), Xinqiao Street 83, Shapingba District, Chongqing, 400037, China.
Bi X; Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), China.
Yang K; Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), China.
Huang Y; Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), China.
Liu Y; Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), China.
Zhao J; Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), China. Electronic address: .
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Źródło:
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Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2020 Oct 15; Vol. 531 (2), pp. 187-194. Date of Electronic Publication: 2020 Aug 09.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: <2002- >: San Diego, CA : Elsevier
Original Publication: New York, Academic Press.
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MeSH Terms:
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Cellular Senescence*
Lamin Type B/*metabolism
Muscle, Smooth, Vascular/*pathology
Myocytes, Smooth Muscle/*pathology
Reactive Oxygen Species/*metabolism
Renal Insufficiency, Chronic/*pathology
p38 Mitogen-Activated Protein Kinases/*metabolism
Animals ; Cell Line ; Cell Nucleus/metabolism ; Humans ; Mice, Inbred C57BL ; Plaque, Atherosclerotic/pathology ; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors
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Contributed Indexing:
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Keywords: Atherosclerotic plaque vulnerability; Cardiovascular diseases; Chronic kidney disease; Lamin B1; Vascular smooth muscle cells
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Substance Nomenclature:
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0 (Lamin Type B)
0 (Reactive Oxygen Species)
EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
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Entry Date(s):
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Date Created: 20200814 Date Completed: 20210309 Latest Revision: 20231213
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Update Code:
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20240105
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DOI:
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10.1016/j.bbrc.2020.07.020
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PMID:
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32788068
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The incidence of cardiovascular thrombotic events which are highly associated with atherosclerotic plaque vulnerability and its rupture is much higher in chronic kidney disease (CKD) patients than that in the general population. It has been reported that the thinning of fibrous cap in atherosclerotic plaque is a crucial factor in plaque vulnerability and thrombosis. Moreover, vascular smooth muscle cells (VSMCs) senescence play a crucial role in maintaining the thickness of fibrous cap. Lamin B1, one of the members of laminin family, is an important component of the nuclear membrane and it is related to cell senescence. While whether lamin B1 participates CKD-related VSMCs senescence and plaque vulnerability and the underlying mechanism remain unclear. Here, we found that CKD promoted fibrous cap thinning and reduced the stability of atherosclerotic plaque through accelerating VSMCs senescence. VSMCs senescence induced by CKD was related to the increased expression of lamin B1 and abnormality of nuclear membrane structure. Knocking down the expression of lamin B1 with RNA interference prevented CKD-induced aberrant nuclear membrane structure and senescence in VSMCs. Additionally, overproduction of reactive oxidative stress (ROS) and subsequent activation of ROS/p38MAPK under CKD milieus contribute to these series of outcomes, as scavenging ROS with N-acety-l-cysteine (NAC) or inhibiting p38MAPK signal pathway with SB203580 could inhibit CKD-induced activation of ROS/p38MAPK, increased expression of lamin B1, abnormality of nuclear membrane structure and VSMCs senescence. Taken together, these results suggested that ROS/p38MAPK-mediated increased expression of lamin B1 and abnormality of nuclear membrane structure was an important mechanism of CKD-induced VSMCs senescence.
Competing Interests: Declaration of competing interest All the authors declared no competing interests.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
