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Tytuł:
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Suppression of NADPH oxidase 4 inhibits PM 2.5 -induced cardiac fibrosis through ROS-P38 MAPK pathway.
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Autorzy:
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Wu M; College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China; Department of Children and Adolescences Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China. Electronic address: .
Xing Q; College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
Duan H; College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
Qin G; College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China. Electronic address: .
Sang N; College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China. Electronic address: .
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Źródło:
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The Science of the total environment [Sci Total Environ] 2022 Sep 01; Vol. 837, pp. 155558. Date of Electronic Publication: 2022 Apr 30.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Original Publication: Amsterdam, Elsevier.
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MeSH Terms:
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MAP Kinase Signaling System*
Myocardium*/metabolism
Myocardium*/pathology
NADPH Oxidase 4*/antagonists & inhibitors
NADPH Oxidase 4*/metabolism
Reactive Oxygen Species*/metabolism
p38 Mitogen-Activated Protein Kinases*/metabolism
Acetophenones/pharmacology ; Animals ; Female ; Fibrosis ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Particulate Matter/toxicity ; RNA, Small Interfering/metabolism ; RNA, Small Interfering/pharmacology ; Transforming Growth Factor beta/metabolism
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Contributed Indexing:
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Keywords: Cardiac; Fibrosis; Fine particulate matter; Molecular mechanism
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Substance Nomenclature:
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0 (Acetophenones)
0 (Particulate Matter)
0 (RNA, Small Interfering)
0 (Reactive Oxygen Species)
0 (Transforming Growth Factor beta)
B6J7B9UDTR (acetovanillone)
EC 1.6.3.- (NADPH Oxidase 4)
EC 1.6.3.- (Nox4 protein, mouse)
EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
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Entry Date(s):
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Date Created: 20220503 Date Completed: 20220610 Latest Revision: 20220616
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Update Code:
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20240104
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DOI:
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10.1016/j.scitotenv.2022.155558
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PMID:
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35504386
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Fine particulate matter (PM 2.5 ) has been consistently linked to cardiovascular diseases, and cardiac fibrosis plays a crucial role in the occurrence and development of heart diseases. It is reported that NOX4-dependent redox signaling are responsible for TGFβ-mediated profibrotic responses. The current study was designed to explore the possible mechanisms of cardiac fibrosis by PM 2.5 both in vitro and in vivo. Female C57BL/6 mice received PM 2.5 (3 mg/kg b.w.) exposure with/without NOX4 inhibitor (apocynin, 25 mg/kg b.w.) or ROS scavenger (NALC, 50 mg/kg b.w.), every other day, for 4 weeks. H9C2 cells were incubated with PM 2.5 (3 μg/mL) with/without 5 mM NALC, TGFβ inhibitor (SB431542, 10 μM), or siRNA-NOX4 for 24 h. The results demonstrated that PM 2.5 induced evident collagen deposition and elevated expression of fibrosis biomarkers (Col1a1 & Col3a1). Significant systemic inflammatory response and cardiac oxidative stress were triggered by PM 2.5 . PM 2.5 increased the protein expression of TGFβ1, NOX4, and P38 MAPK. Notably, the increased effects of PM 2.5 could be suppressed by SB431542, siRNA-NOX4 in vitro or apocynin in vivo, and NALC. The reverse verification experiments further supported the involvement of the TGFβ/NOX4/ROS/P38 MAPK signaling pathway in the myocardial fibrosis induced by PM 2.5 . In summary, the current study provided evidence that PM 2.5 challenge led to cardiac fibrosis through oxidative stress, systemic inflammation, and subsequent TGFβ/NOX4/ROS/P38 MAPK pathway and may offer new therapeutic targets in cardiac fibrosis.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier B.V. All rights reserved.)