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MiR-148a-3p within HucMSC-Derived Extracellular Vesicles Suppresses Hsp90b1 to Prevent Fibroblast Collagen Synthesis and Secretion in Silica-Induced Pulmonary Fibrosis

Silicosis is a fatal occupational respiratory disease caused by the prolonged inhalation of respirable silica. The core event of silicosis is the heightened activity of fibroblasts, which excessively synthesize extracellular matrix (ECM) proteins. Our previous studies have highlighted that human umb...

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Autores principales: Jiang, Qiyue, Zhao, Jing, Jia, Qiyue, Wang, Hongwei, Xue, Wenming, Ning, Fuao, Wang, Jiaxin, Wang, Yan, Zhu, Zhonghui, Tian, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10572270/
https://www.ncbi.nlm.nih.gov/pubmed/37833927
http://dx.doi.org/10.3390/ijms241914477
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author Jiang, Qiyue
Zhao, Jing
Jia, Qiyue
Wang, Hongwei
Xue, Wenming
Ning, Fuao
Wang, Jiaxin
Wang, Yan
Zhu, Zhonghui
Tian, Lin
author_facet Jiang, Qiyue
Zhao, Jing
Jia, Qiyue
Wang, Hongwei
Xue, Wenming
Ning, Fuao
Wang, Jiaxin
Wang, Yan
Zhu, Zhonghui
Tian, Lin
author_sort Jiang, Qiyue
collection PubMed
description Silicosis is a fatal occupational respiratory disease caused by the prolonged inhalation of respirable silica. The core event of silicosis is the heightened activity of fibroblasts, which excessively synthesize extracellular matrix (ECM) proteins. Our previous studies have highlighted that human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs) hold promise in mitigating silicosis and the significant role played by microRNAs (miRNAs) in this process. Delving deeper into this mechanism, we found that miR-148a-3p was the most abundant miRNA of the differential miRNAs in hucMSC-EVs, with the gene heat shock protein 90 beta family member 1 (Hsp90b1) as a potential target. Notably, miR-148a-3p’s expression was downregulated during the progression of silica-induced pulmonary fibrosis both in vitro and in vivo, but was restored after hucMSC-EVs treatment (p < 0.05). Introducing miR-148a-3p mimics effectively hindered the collagen synthesis and secretion of fibroblasts induced by transforming growth factor-β1 (TGF-β1) (p < 0.05). Confirming our hypothesis, Hsp90b1 was indeed targeted by miR-148a-3p, with significantly reduced collagen activity in TGF-β1-treated fibroblasts upon Hsp90b1 inhibition (p < 0.05). Collectively, our findings provide compelling evidence that links miR-148a-3p present in hucMSC-EVs with the amelioration of silicosis, suggesting its therapeutic potential by specifically targeting Hsp90b1, thereby inhibiting fibroblast collagen activities. This study sheds light on the role of miR-148a-3p in hucMSC-EVs, opening avenues for innovative therapeutic interventions targeting molecular pathways in pulmonary fibrosis.
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spelling pubmed-105722702023-10-14 MiR-148a-3p within HucMSC-Derived Extracellular Vesicles Suppresses Hsp90b1 to Prevent Fibroblast Collagen Synthesis and Secretion in Silica-Induced Pulmonary Fibrosis Jiang, Qiyue Zhao, Jing Jia, Qiyue Wang, Hongwei Xue, Wenming Ning, Fuao Wang, Jiaxin Wang, Yan Zhu, Zhonghui Tian, Lin Int J Mol Sci Article Silicosis is a fatal occupational respiratory disease caused by the prolonged inhalation of respirable silica. The core event of silicosis is the heightened activity of fibroblasts, which excessively synthesize extracellular matrix (ECM) proteins. Our previous studies have highlighted that human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs) hold promise in mitigating silicosis and the significant role played by microRNAs (miRNAs) in this process. Delving deeper into this mechanism, we found that miR-148a-3p was the most abundant miRNA of the differential miRNAs in hucMSC-EVs, with the gene heat shock protein 90 beta family member 1 (Hsp90b1) as a potential target. Notably, miR-148a-3p’s expression was downregulated during the progression of silica-induced pulmonary fibrosis both in vitro and in vivo, but was restored after hucMSC-EVs treatment (p < 0.05). Introducing miR-148a-3p mimics effectively hindered the collagen synthesis and secretion of fibroblasts induced by transforming growth factor-β1 (TGF-β1) (p < 0.05). Confirming our hypothesis, Hsp90b1 was indeed targeted by miR-148a-3p, with significantly reduced collagen activity in TGF-β1-treated fibroblasts upon Hsp90b1 inhibition (p < 0.05). Collectively, our findings provide compelling evidence that links miR-148a-3p present in hucMSC-EVs with the amelioration of silicosis, suggesting its therapeutic potential by specifically targeting Hsp90b1, thereby inhibiting fibroblast collagen activities. This study sheds light on the role of miR-148a-3p in hucMSC-EVs, opening avenues for innovative therapeutic interventions targeting molecular pathways in pulmonary fibrosis. MDPI 2023-09-23 /pmc/articles/PMC10572270/ /pubmed/37833927 http://dx.doi.org/10.3390/ijms241914477 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
Jiang, Qiyue
Zhao, Jing
Jia, Qiyue
Wang, Hongwei
Xue, Wenming
Ning, Fuao
Wang, Jiaxin
Wang, Yan
Zhu, Zhonghui
Tian, Lin
MiR-148a-3p within HucMSC-Derived Extracellular Vesicles Suppresses Hsp90b1 to Prevent Fibroblast Collagen Synthesis and Secretion in Silica-Induced Pulmonary Fibrosis
title MiR-148a-3p within HucMSC-Derived Extracellular Vesicles Suppresses Hsp90b1 to Prevent Fibroblast Collagen Synthesis and Secretion in Silica-Induced Pulmonary Fibrosis
title_full MiR-148a-3p within HucMSC-Derived Extracellular Vesicles Suppresses Hsp90b1 to Prevent Fibroblast Collagen Synthesis and Secretion in Silica-Induced Pulmonary Fibrosis
title_fullStr MiR-148a-3p within HucMSC-Derived Extracellular Vesicles Suppresses Hsp90b1 to Prevent Fibroblast Collagen Synthesis and Secretion in Silica-Induced Pulmonary Fibrosis
title_full_unstemmed MiR-148a-3p within HucMSC-Derived Extracellular Vesicles Suppresses Hsp90b1 to Prevent Fibroblast Collagen Synthesis and Secretion in Silica-Induced Pulmonary Fibrosis
title_short MiR-148a-3p within HucMSC-Derived Extracellular Vesicles Suppresses Hsp90b1 to Prevent Fibroblast Collagen Synthesis and Secretion in Silica-Induced Pulmonary Fibrosis
title_sort mir-148a-3p within hucmsc-derived extracellular vesicles suppresses hsp90b1 to prevent fibroblast collagen synthesis and secretion in silica-induced pulmonary fibrosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10572270/
https://www.ncbi.nlm.nih.gov/pubmed/37833927
http://dx.doi.org/10.3390/ijms241914477
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