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Regulating the cell shift of endothelial cell-like myofibroblasts in pulmonary fibrosis

Pulmonary fibrosis is a common and severe fibrotic lung disease with high morbidity and mortality. Recent studies have reported a large number of unwanted myofibroblasts appearing in pulmonary fibrosis, and shown that the sustained activation of myofibroblasts is essential for unremitting interstiti...

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Autores principales: Wu, Xiuju, Zhang, Daoqin, Qiao, Xiaojing, Zhang, Li, Cai, Xinjiang, Ji, Jaden, Ma, Jocelyn A., Zhao, Yan, Belperio, John A., Boström, Kristina I., Yao, Yucheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: European Respiratory Society 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10249020/
https://www.ncbi.nlm.nih.gov/pubmed/36758986
http://dx.doi.org/10.1183/13993003.01799-2022
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author Wu, Xiuju
Zhang, Daoqin
Qiao, Xiaojing
Zhang, Li
Cai, Xinjiang
Ji, Jaden
Ma, Jocelyn A.
Zhao, Yan
Belperio, John A.
Boström, Kristina I.
Yao, Yucheng
author_facet Wu, Xiuju
Zhang, Daoqin
Qiao, Xiaojing
Zhang, Li
Cai, Xinjiang
Ji, Jaden
Ma, Jocelyn A.
Zhao, Yan
Belperio, John A.
Boström, Kristina I.
Yao, Yucheng
author_sort Wu, Xiuju
collection PubMed
description Pulmonary fibrosis is a common and severe fibrotic lung disease with high morbidity and mortality. Recent studies have reported a large number of unwanted myofibroblasts appearing in pulmonary fibrosis, and shown that the sustained activation of myofibroblasts is essential for unremitting interstitial fibrogenesis. However, the origin of these myofibroblasts remains poorly understood. Here, we create new mouse models of pulmonary fibrosis and identify a previously unknown population of endothelial cell (EC)-like myofibroblasts in normal lung tissue. We show that these EC-like myofibroblasts significantly contribute myofibroblasts to pulmonary fibrosis, which is confirmed by single-cell RNA sequencing of human pulmonary fibrosis. Using the transcriptional profiles, we identified a small molecule that redirects the differentiation of EC-like myofibroblasts and reduces pulmonary fibrosis in our mouse models. Our study reveals the mechanistic underpinnings of the differentiation of EC-like myofibroblasts in pulmonary fibrosis and may provide new strategies for therapeutic interventions.
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spelling pubmed-102490202023-06-09 Regulating the cell shift of endothelial cell-like myofibroblasts in pulmonary fibrosis Wu, Xiuju Zhang, Daoqin Qiao, Xiaojing Zhang, Li Cai, Xinjiang Ji, Jaden Ma, Jocelyn A. Zhao, Yan Belperio, John A. Boström, Kristina I. Yao, Yucheng Eur Respir J Original Research Articles Pulmonary fibrosis is a common and severe fibrotic lung disease with high morbidity and mortality. Recent studies have reported a large number of unwanted myofibroblasts appearing in pulmonary fibrosis, and shown that the sustained activation of myofibroblasts is essential for unremitting interstitial fibrogenesis. However, the origin of these myofibroblasts remains poorly understood. Here, we create new mouse models of pulmonary fibrosis and identify a previously unknown population of endothelial cell (EC)-like myofibroblasts in normal lung tissue. We show that these EC-like myofibroblasts significantly contribute myofibroblasts to pulmonary fibrosis, which is confirmed by single-cell RNA sequencing of human pulmonary fibrosis. Using the transcriptional profiles, we identified a small molecule that redirects the differentiation of EC-like myofibroblasts and reduces pulmonary fibrosis in our mouse models. Our study reveals the mechanistic underpinnings of the differentiation of EC-like myofibroblasts in pulmonary fibrosis and may provide new strategies for therapeutic interventions. European Respiratory Society 2023-06-08 /pmc/articles/PMC10249020/ /pubmed/36758986 http://dx.doi.org/10.1183/13993003.01799-2022 Text en Copyright ©The authors 2023. https://creativecommons.org/licenses/by-nc/4.0/This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org (mailto:permissions@ersnet.org)
spellingShingle Original Research Articles
Wu, Xiuju
Zhang, Daoqin
Qiao, Xiaojing
Zhang, Li
Cai, Xinjiang
Ji, Jaden
Ma, Jocelyn A.
Zhao, Yan
Belperio, John A.
Boström, Kristina I.
Yao, Yucheng
Regulating the cell shift of endothelial cell-like myofibroblasts in pulmonary fibrosis
title Regulating the cell shift of endothelial cell-like myofibroblasts in pulmonary fibrosis
title_full Regulating the cell shift of endothelial cell-like myofibroblasts in pulmonary fibrosis
title_fullStr Regulating the cell shift of endothelial cell-like myofibroblasts in pulmonary fibrosis
title_full_unstemmed Regulating the cell shift of endothelial cell-like myofibroblasts in pulmonary fibrosis
title_short Regulating the cell shift of endothelial cell-like myofibroblasts in pulmonary fibrosis
title_sort regulating the cell shift of endothelial cell-like myofibroblasts in pulmonary fibrosis
topic Original Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10249020/
https://www.ncbi.nlm.nih.gov/pubmed/36758986
http://dx.doi.org/10.1183/13993003.01799-2022
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