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Inhibition of Mitofusin-2 Promotes Cardiac Fibroblast Activation via the PERKATF4 Pathway and Reactive Oxygen Species
Joint Authors
Wu, Wenchao
Liu, Xiaojing
Xin, Yanguo
Qu, Jing
Wang, Xiaojiao
Lei, Song
Yuan, Lixing
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-04-16
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
Mitofusin-2 (Mfn2) is a key outer mitochondrial membrane protein, which maintains normal mitochondrial dynamics and function.
However, its role in cardiac fibroblast activation remains poorly understood.
In the present study, a rat model of transverse aortic constriction (TAC) was established to observe the cardiac fibroblast activation in vivo.
TGF-β1 treatment for 24 hours was used to induce cardiac fibroblast activation in vitro.
As a result, the expression of Mfn2 decreased in the hypertrophic heart tissues and cardiac fibroblasts treated with TGF-β1.
siMfn2 and adenovirus were applied to mediate Mfn2 gene silencing and overexpression in cardiac fibroblasts to elucidate the relationship between Mfn2 and cardiac fibroblast activation, as well as the possible underlying mechanisms.
Knockdown of Mfn2 further promoted TGF-β1-induced cardiac fibroblast activation, while forced expression of Mfn2 attenuated this pathological reaction.
The PERK/ATF4 pathway, one of the branches of endoplasmic reticulum (ER) stress, was identified to be involved in this process.
Knockdown and overexpression of Mfn2 lead to aggravation or alleviation of the PERK/ATF4 pathway.
Blocking this pathway by silencing ATF4 with siATF4 attenuated the pathological process.
During the activation of cardiac fibroblasts, knockdown of Mfn2 also increased the production of reactive oxygen species (ROS), while ROS scavenger N-acetyl-l-cysteine (NAC) could attenuate the effect caused by knockdown of Mfn2.
Our data suggested that inhibition of Mfn2 could promote cardiac fibroblast activation by activating the PERK/ATF4 signaling pathway and increasing the generation of ROS.
American Psychological Association (APA)
Xin, Yanguo& Wu, Wenchao& Qu, Jing& Wang, Xiaojiao& Lei, Song& Yuan, Lixing…[et al.]. 2019. Inhibition of Mitofusin-2 Promotes Cardiac Fibroblast Activation via the PERKATF4 Pathway and Reactive Oxygen Species. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-16.
https://search.emarefa.net/detail/BIM-1203328
Modern Language Association (MLA)
Xin, Yanguo…[et al.]. Inhibition of Mitofusin-2 Promotes Cardiac Fibroblast Activation via the PERKATF4 Pathway and Reactive Oxygen Species. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-16.
https://search.emarefa.net/detail/BIM-1203328
American Medical Association (AMA)
Xin, Yanguo& Wu, Wenchao& Qu, Jing& Wang, Xiaojiao& Lei, Song& Yuan, Lixing…[et al.]. Inhibition of Mitofusin-2 Promotes Cardiac Fibroblast Activation via the PERKATF4 Pathway and Reactive Oxygen Species. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-16.
https://search.emarefa.net/detail/BIM-1203328
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1203328