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Catalpol Attenuates Pulmonary Fibrosis by Inhibiting Ang II/AT(1) and TGF-β/Smad-Mediated Epithelial Mesenchymal Transition
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and devastating chronic lung condition affecting over 3 million people worldwide with a high mortality rate and there are no effective drugs. Angiotensin II (Ang II), as a major effector peptide of the renin angiotensin aldosterone sys...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171363/ https://www.ncbi.nlm.nih.gov/pubmed/35685407 http://dx.doi.org/10.3389/fmed.2022.878601 |
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author | Yu, Qun Zhu, Dewei Zou, Yang Wang, Kai Rao, Peili Shen, Yunhui |
author_facet | Yu, Qun Zhu, Dewei Zou, Yang Wang, Kai Rao, Peili Shen, Yunhui |
author_sort | Yu, Qun |
collection | PubMed |
description | BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and devastating chronic lung condition affecting over 3 million people worldwide with a high mortality rate and there are no effective drugs. Angiotensin II (Ang II), as a major effector peptide of the renin angiotensin aldosterone system, has been shown to act in tandem with the transforming growth factor-β (TGF-β) signaling pathway to promote the infiltration of inflammatory cells, production of reactive oxygen species (ROS) and profibrotic factors after lung injury, and to participate in the process of epithelial mesenchymal transition (EMT). Catalpol (CAT) has been shown to have anti-inflammatory and antifibrotic effects. However, the effects and mechanisms of CAT on pulmonary fibrosis are not clear. PURPOSE: To assess the effects and mechanisms of catalpol on bleomycin-induced pulmonary fibrosis in mice. METHODS: We used bleomycin-induced mouse model of pulmonary fibrosis to evaluate the alleviation effect of CAT at 7, 14, 28d, respectively. Next, enzyme-linked immunosorbent assay, hematoxylin-eosin staining, immunofluorescence, Masson trichrome staining and western blotting were used to study the underlying mechanism of CAT on bleomycin-induced pulmonary fibrosis. RESULTS: It's demonstrated that CAT exerted a potent anti-fibrotic function in BLM-induced mice pulmonary fibrosis via alleviating inflammatory, ameliorating collagen deposition, reducing the level of Ang II and HYP and alleviating the degree of EMT. Moreover, CAT attenuate BLM-induced fibrosis by targeting Ang II/AT(1) and TGF-β/Smad signaling in vivo. CONCLUSION: CAT may serve as a novel therapeutic candidate for the simultaneous blockade of Ang II and TGF-β pathway to attenuate pulmonary fibrosis. |
format | Online Article Text |
id | pubmed-9171363 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91713632022-06-08 Catalpol Attenuates Pulmonary Fibrosis by Inhibiting Ang II/AT(1) and TGF-β/Smad-Mediated Epithelial Mesenchymal Transition Yu, Qun Zhu, Dewei Zou, Yang Wang, Kai Rao, Peili Shen, Yunhui Front Med (Lausanne) Medicine BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and devastating chronic lung condition affecting over 3 million people worldwide with a high mortality rate and there are no effective drugs. Angiotensin II (Ang II), as a major effector peptide of the renin angiotensin aldosterone system, has been shown to act in tandem with the transforming growth factor-β (TGF-β) signaling pathway to promote the infiltration of inflammatory cells, production of reactive oxygen species (ROS) and profibrotic factors after lung injury, and to participate in the process of epithelial mesenchymal transition (EMT). Catalpol (CAT) has been shown to have anti-inflammatory and antifibrotic effects. However, the effects and mechanisms of CAT on pulmonary fibrosis are not clear. PURPOSE: To assess the effects and mechanisms of catalpol on bleomycin-induced pulmonary fibrosis in mice. METHODS: We used bleomycin-induced mouse model of pulmonary fibrosis to evaluate the alleviation effect of CAT at 7, 14, 28d, respectively. Next, enzyme-linked immunosorbent assay, hematoxylin-eosin staining, immunofluorescence, Masson trichrome staining and western blotting were used to study the underlying mechanism of CAT on bleomycin-induced pulmonary fibrosis. RESULTS: It's demonstrated that CAT exerted a potent anti-fibrotic function in BLM-induced mice pulmonary fibrosis via alleviating inflammatory, ameliorating collagen deposition, reducing the level of Ang II and HYP and alleviating the degree of EMT. Moreover, CAT attenuate BLM-induced fibrosis by targeting Ang II/AT(1) and TGF-β/Smad signaling in vivo. CONCLUSION: CAT may serve as a novel therapeutic candidate for the simultaneous blockade of Ang II and TGF-β pathway to attenuate pulmonary fibrosis. Frontiers Media S.A. 2022-05-24 /pmc/articles/PMC9171363/ /pubmed/35685407 http://dx.doi.org/10.3389/fmed.2022.878601 Text en Copyright © 2022 Yu, Zhu, Zou, Wang, Rao and Shen. 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 | Medicine Yu, Qun Zhu, Dewei Zou, Yang Wang, Kai Rao, Peili Shen, Yunhui Catalpol Attenuates Pulmonary Fibrosis by Inhibiting Ang II/AT(1) and TGF-β/Smad-Mediated Epithelial Mesenchymal Transition |
title | Catalpol Attenuates Pulmonary Fibrosis by Inhibiting Ang II/AT(1) and TGF-β/Smad-Mediated Epithelial Mesenchymal Transition |
title_full | Catalpol Attenuates Pulmonary Fibrosis by Inhibiting Ang II/AT(1) and TGF-β/Smad-Mediated Epithelial Mesenchymal Transition |
title_fullStr | Catalpol Attenuates Pulmonary Fibrosis by Inhibiting Ang II/AT(1) and TGF-β/Smad-Mediated Epithelial Mesenchymal Transition |
title_full_unstemmed | Catalpol Attenuates Pulmonary Fibrosis by Inhibiting Ang II/AT(1) and TGF-β/Smad-Mediated Epithelial Mesenchymal Transition |
title_short | Catalpol Attenuates Pulmonary Fibrosis by Inhibiting Ang II/AT(1) and TGF-β/Smad-Mediated Epithelial Mesenchymal Transition |
title_sort | catalpol attenuates pulmonary fibrosis by inhibiting ang ii/at(1) and tgf-β/smad-mediated epithelial mesenchymal transition |
topic | Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171363/ https://www.ncbi.nlm.nih.gov/pubmed/35685407 http://dx.doi.org/10.3389/fmed.2022.878601 |
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