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Baricitinib Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice by Inhibiting TGF-β1 Signaling Pathway

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease with unknown etiology, high mortality and limited treatment options. It is characterized by myofibroblast proliferation and extensive deposition of extracellular matrix (ECM), which will lead to fibrous proliferat...

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Autores principales: Gu, Songtao, Liang, Jingjing, Zhang, Jianwei, Liu, Zhichao, Miao, Yang, Wei, Yuli, Li, Shimeng, Gu, Jinying, Cui, Yunyao, Xiao, Ting, Li, Xiaohe, Yang, Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10004526/
https://www.ncbi.nlm.nih.gov/pubmed/36903446
http://dx.doi.org/10.3390/molecules28052195
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author Gu, Songtao
Liang, Jingjing
Zhang, Jianwei
Liu, Zhichao
Miao, Yang
Wei, Yuli
Li, Shimeng
Gu, Jinying
Cui, Yunyao
Xiao, Ting
Li, Xiaohe
Yang, Cheng
author_facet Gu, Songtao
Liang, Jingjing
Zhang, Jianwei
Liu, Zhichao
Miao, Yang
Wei, Yuli
Li, Shimeng
Gu, Jinying
Cui, Yunyao
Xiao, Ting
Li, Xiaohe
Yang, Cheng
author_sort Gu, Songtao
collection PubMed
description Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease with unknown etiology, high mortality and limited treatment options. It is characterized by myofibroblast proliferation and extensive deposition of extracellular matrix (ECM), which will lead to fibrous proliferation and the destruction of lung structure. Transforming growth factor-β1 (TGF-β1) is widely recognized as a central pathway of pulmonary fibrosis, and the suppression of TGF-β1 or the TGF-β1-regulated signaling pathway may thus offer potential antifibrotic therapies. JAK-STAT is a downstream signaling pathway regulated by TGF-β1. JAK1/2 inhibitor baricitinib is a marketed drug for the treatment of rheumatoid arthritis, but its role in pulmonary fibrosis has not been reported. This study explored the potential effect and mechanism of baricitinib on pulmonary fibrosis in vivo and in vitro. The in vivo studies have shown that baricitinib can effectively attenuate bleomycin (BLM)-induced pulmonary fibrosis, and in vitro studies showed that baricitinib attenuates TGF-β1-induced fibroblast activation and epithelial cell injury by inhibiting TGF-β1/non-Smad and TGF-β1/JAK/STAT signaling pathways, respectively. In conclusion, baricitinib, a JAK1/2 inhibitor, impedes myofibroblast activation and epithelial injury via targeting the TGF-β1 signaling pathway and reduces BLM-induced pulmonary fibrosis in mice.
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spelling pubmed-100045262023-03-11 Baricitinib Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice by Inhibiting TGF-β1 Signaling Pathway Gu, Songtao Liang, Jingjing Zhang, Jianwei Liu, Zhichao Miao, Yang Wei, Yuli Li, Shimeng Gu, Jinying Cui, Yunyao Xiao, Ting Li, Xiaohe Yang, Cheng Molecules Article Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease with unknown etiology, high mortality and limited treatment options. It is characterized by myofibroblast proliferation and extensive deposition of extracellular matrix (ECM), which will lead to fibrous proliferation and the destruction of lung structure. Transforming growth factor-β1 (TGF-β1) is widely recognized as a central pathway of pulmonary fibrosis, and the suppression of TGF-β1 or the TGF-β1-regulated signaling pathway may thus offer potential antifibrotic therapies. JAK-STAT is a downstream signaling pathway regulated by TGF-β1. JAK1/2 inhibitor baricitinib is a marketed drug for the treatment of rheumatoid arthritis, but its role in pulmonary fibrosis has not been reported. This study explored the potential effect and mechanism of baricitinib on pulmonary fibrosis in vivo and in vitro. The in vivo studies have shown that baricitinib can effectively attenuate bleomycin (BLM)-induced pulmonary fibrosis, and in vitro studies showed that baricitinib attenuates TGF-β1-induced fibroblast activation and epithelial cell injury by inhibiting TGF-β1/non-Smad and TGF-β1/JAK/STAT signaling pathways, respectively. In conclusion, baricitinib, a JAK1/2 inhibitor, impedes myofibroblast activation and epithelial injury via targeting the TGF-β1 signaling pathway and reduces BLM-induced pulmonary fibrosis in mice. MDPI 2023-02-27 /pmc/articles/PMC10004526/ /pubmed/36903446 http://dx.doi.org/10.3390/molecules28052195 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gu, Songtao
Liang, Jingjing
Zhang, Jianwei
Liu, Zhichao
Miao, Yang
Wei, Yuli
Li, Shimeng
Gu, Jinying
Cui, Yunyao
Xiao, Ting
Li, Xiaohe
Yang, Cheng
Baricitinib Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice by Inhibiting TGF-β1 Signaling Pathway
title Baricitinib Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice by Inhibiting TGF-β1 Signaling Pathway
title_full Baricitinib Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice by Inhibiting TGF-β1 Signaling Pathway
title_fullStr Baricitinib Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice by Inhibiting TGF-β1 Signaling Pathway
title_full_unstemmed Baricitinib Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice by Inhibiting TGF-β1 Signaling Pathway
title_short Baricitinib Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice by Inhibiting TGF-β1 Signaling Pathway
title_sort baricitinib attenuates bleomycin-induced pulmonary fibrosis in mice by inhibiting tgf-β1 signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10004526/
https://www.ncbi.nlm.nih.gov/pubmed/36903446
http://dx.doi.org/10.3390/molecules28052195
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