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Bellidifolin Ameliorates Isoprenaline-Induced Myocardial Fibrosis by Regulating TGF-β1/Smads and p38 Signaling and Preventing NR4A1 Cytoplasmic Localization

Myocardial fibrosis is closely related to high morbidity and mortality. In Inner Mongolia, Gentianella amarella subsp. acuta (Michx.) J.M.Gillett (G. acuta) is a kind of tea used to prevent cardiovascular diseases. Bellidifolin (BEL) is an active xanthone molecule from G. acuta that protects against...

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Autores principales: Yang, Hong-Xia, Sun, Jia-Huan, Yao, Ting-Ting, Li, Yuan, Xu, Geng-Rui, Zhang, Chuang, Liu, Xing-Chao, Zhou, Wei-Wei, Song, Qiu-Hang, Zhang, Yue, Li, Ai-Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120298/
https://www.ncbi.nlm.nih.gov/pubmed/33995055
http://dx.doi.org/10.3389/fphar.2021.644886
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author Yang, Hong-Xia
Sun, Jia-Huan
Yao, Ting-Ting
Li, Yuan
Xu, Geng-Rui
Zhang, Chuang
Liu, Xing-Chao
Zhou, Wei-Wei
Song, Qiu-Hang
Zhang, Yue
Li, Ai-Ying
author_facet Yang, Hong-Xia
Sun, Jia-Huan
Yao, Ting-Ting
Li, Yuan
Xu, Geng-Rui
Zhang, Chuang
Liu, Xing-Chao
Zhou, Wei-Wei
Song, Qiu-Hang
Zhang, Yue
Li, Ai-Ying
author_sort Yang, Hong-Xia
collection PubMed
description Myocardial fibrosis is closely related to high morbidity and mortality. In Inner Mongolia, Gentianella amarella subsp. acuta (Michx.) J.M.Gillett (G. acuta) is a kind of tea used to prevent cardiovascular diseases. Bellidifolin (BEL) is an active xanthone molecule from G. acuta that protects against myocardial damage. However, the effects and mechanisms of BEL on myocardial fibrosis have not been reported. In vivo, BEL dampened isoprenaline (ISO)-induced cardiac structure disturbance and collagen deposition. In vitro, BEL inhibited transforming growth factor (TGF)-β1-induced cardiac fibroblast (CF) proliferation. In vivo and in vitro, BEL decreased the expression of α-smooth muscle actin (α-SMA), collagen Ⅰ and Ⅲ, and inhibited TGF-β1/Smads signaling. Additionally, BEL impeded p38 activation and NR4A1 (an endogenous inhibitor for pro-fibrogenic activities of TGF-β1) phosphorylation and inactivation in vitro. In CFs, inhibition of p38 by SB203580 inhibited the phosphorylation of NR4A1 and did not limit Smad3 phosphorylation, and blocking TGF-β signaling by LY2157299 and SB203580 could decrease the expression of α-SMA, collagen I and III. Overall, both cell and animal studies provide a potential role for BEL against myocardial fibrosis by inhibiting the proliferation and phenotypic transformation of CFs. These inhibitory effects might be related to regulating TGF-β1/Smads pathway and p38 signaling and preventing NR4A1 cytoplasmic localization.
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spelling pubmed-81202982021-05-15 Bellidifolin Ameliorates Isoprenaline-Induced Myocardial Fibrosis by Regulating TGF-β1/Smads and p38 Signaling and Preventing NR4A1 Cytoplasmic Localization Yang, Hong-Xia Sun, Jia-Huan Yao, Ting-Ting Li, Yuan Xu, Geng-Rui Zhang, Chuang Liu, Xing-Chao Zhou, Wei-Wei Song, Qiu-Hang Zhang, Yue Li, Ai-Ying Front Pharmacol Pharmacology Myocardial fibrosis is closely related to high morbidity and mortality. In Inner Mongolia, Gentianella amarella subsp. acuta (Michx.) J.M.Gillett (G. acuta) is a kind of tea used to prevent cardiovascular diseases. Bellidifolin (BEL) is an active xanthone molecule from G. acuta that protects against myocardial damage. However, the effects and mechanisms of BEL on myocardial fibrosis have not been reported. In vivo, BEL dampened isoprenaline (ISO)-induced cardiac structure disturbance and collagen deposition. In vitro, BEL inhibited transforming growth factor (TGF)-β1-induced cardiac fibroblast (CF) proliferation. In vivo and in vitro, BEL decreased the expression of α-smooth muscle actin (α-SMA), collagen Ⅰ and Ⅲ, and inhibited TGF-β1/Smads signaling. Additionally, BEL impeded p38 activation and NR4A1 (an endogenous inhibitor for pro-fibrogenic activities of TGF-β1) phosphorylation and inactivation in vitro. In CFs, inhibition of p38 by SB203580 inhibited the phosphorylation of NR4A1 and did not limit Smad3 phosphorylation, and blocking TGF-β signaling by LY2157299 and SB203580 could decrease the expression of α-SMA, collagen I and III. Overall, both cell and animal studies provide a potential role for BEL against myocardial fibrosis by inhibiting the proliferation and phenotypic transformation of CFs. These inhibitory effects might be related to regulating TGF-β1/Smads pathway and p38 signaling and preventing NR4A1 cytoplasmic localization. Frontiers Media S.A. 2021-04-30 /pmc/articles/PMC8120298/ /pubmed/33995055 http://dx.doi.org/10.3389/fphar.2021.644886 Text en Copyright © 2021 Yang, Sun, Yao, Li, Xu, Zhang, Liu, Zhou, Song, Zhang and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Yang, Hong-Xia
Sun, Jia-Huan
Yao, Ting-Ting
Li, Yuan
Xu, Geng-Rui
Zhang, Chuang
Liu, Xing-Chao
Zhou, Wei-Wei
Song, Qiu-Hang
Zhang, Yue
Li, Ai-Ying
Bellidifolin Ameliorates Isoprenaline-Induced Myocardial Fibrosis by Regulating TGF-β1/Smads and p38 Signaling and Preventing NR4A1 Cytoplasmic Localization
title Bellidifolin Ameliorates Isoprenaline-Induced Myocardial Fibrosis by Regulating TGF-β1/Smads and p38 Signaling and Preventing NR4A1 Cytoplasmic Localization
title_full Bellidifolin Ameliorates Isoprenaline-Induced Myocardial Fibrosis by Regulating TGF-β1/Smads and p38 Signaling and Preventing NR4A1 Cytoplasmic Localization
title_fullStr Bellidifolin Ameliorates Isoprenaline-Induced Myocardial Fibrosis by Regulating TGF-β1/Smads and p38 Signaling and Preventing NR4A1 Cytoplasmic Localization
title_full_unstemmed Bellidifolin Ameliorates Isoprenaline-Induced Myocardial Fibrosis by Regulating TGF-β1/Smads and p38 Signaling and Preventing NR4A1 Cytoplasmic Localization
title_short Bellidifolin Ameliorates Isoprenaline-Induced Myocardial Fibrosis by Regulating TGF-β1/Smads and p38 Signaling and Preventing NR4A1 Cytoplasmic Localization
title_sort bellidifolin ameliorates isoprenaline-induced myocardial fibrosis by regulating tgf-β1/smads and p38 signaling and preventing nr4a1 cytoplasmic localization
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120298/
https://www.ncbi.nlm.nih.gov/pubmed/33995055
http://dx.doi.org/10.3389/fphar.2021.644886
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