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Unraveling FOXO3a and USP18 Functions in Idiopathic Pulmonary Fibrosis through Single-Cell RNA Sequencing of Mouse and Human Lungs
Background Idiopathic pulmonary fibrosis (IPF) is identified as a chronic, progressive lung disease, predominantly marked by enhanced fibroblast proliferation and excessive deposition of extracellular matrix. The intricate interactions between diverse molecular pathways in fibroblasts play a crucia...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Georg Thieme Verlag KG
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651367/ https://www.ncbi.nlm.nih.gov/pubmed/38025194 http://dx.doi.org/10.1055/s-0043-1776697 |
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author | Wang, Ban Pan, Jichun Liu, Zhonghui |
author_facet | Wang, Ban Pan, Jichun Liu, Zhonghui |
author_sort | Wang, Ban |
collection | PubMed |
description | Background Idiopathic pulmonary fibrosis (IPF) is identified as a chronic, progressive lung disease, predominantly marked by enhanced fibroblast proliferation and excessive deposition of extracellular matrix. The intricate interactions between diverse molecular pathways in fibroblasts play a crucial role in driving the pathogenesis of IPF. Methods This research is focused on elucidating the roles of FOXO3a, a transcription factor, and USP18, a ubiquitin-specific protease, in modulating fibroblast functionality in the context of IPF. FOXO3a is well-known for its regulatory effects on cellular responses, including apoptosis and oxidative stress, while USP18 is generally associated with protein deubiquitination. Results Our findings highlight that FOXO3a acts as a critical regulator in controlling fibroblast activation and differentiation, illustrating its vital role in the pathology of IPF. Conversely, USP18 seems to promote fibroblast proliferation and imparts resistance to apoptosis, thereby contributing to the exacerbation of fibrotic processes. The synergistic dysregulation of both FOXO3a and USP18 in fibroblasts was found to significantly contribute to the fibrotic alterations characteristic of IPF. Conclusion Deciphering the complex molecular interactions between FOXO3a and USP18 in fibroblasts provides a deeper understanding of IPF pathogenesis and unveils novel therapeutic avenues, offering a promising potential for not just halting but potentially reversing the progression of this debilitating disease. |
format | Online Article Text |
id | pubmed-10651367 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Georg Thieme Verlag KG |
record_format | MEDLINE/PubMed |
spelling | pubmed-106513672023-11-01 Unraveling FOXO3a and USP18 Functions in Idiopathic Pulmonary Fibrosis through Single-Cell RNA Sequencing of Mouse and Human Lungs Wang, Ban Pan, Jichun Liu, Zhonghui Glob Med Genet Background Idiopathic pulmonary fibrosis (IPF) is identified as a chronic, progressive lung disease, predominantly marked by enhanced fibroblast proliferation and excessive deposition of extracellular matrix. The intricate interactions between diverse molecular pathways in fibroblasts play a crucial role in driving the pathogenesis of IPF. Methods This research is focused on elucidating the roles of FOXO3a, a transcription factor, and USP18, a ubiquitin-specific protease, in modulating fibroblast functionality in the context of IPF. FOXO3a is well-known for its regulatory effects on cellular responses, including apoptosis and oxidative stress, while USP18 is generally associated with protein deubiquitination. Results Our findings highlight that FOXO3a acts as a critical regulator in controlling fibroblast activation and differentiation, illustrating its vital role in the pathology of IPF. Conversely, USP18 seems to promote fibroblast proliferation and imparts resistance to apoptosis, thereby contributing to the exacerbation of fibrotic processes. The synergistic dysregulation of both FOXO3a and USP18 in fibroblasts was found to significantly contribute to the fibrotic alterations characteristic of IPF. Conclusion Deciphering the complex molecular interactions between FOXO3a and USP18 in fibroblasts provides a deeper understanding of IPF pathogenesis and unveils novel therapeutic avenues, offering a promising potential for not just halting but potentially reversing the progression of this debilitating disease. Georg Thieme Verlag KG 2023-11-15 /pmc/articles/PMC10651367/ /pubmed/38025194 http://dx.doi.org/10.1055/s-0043-1776697 Text en The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ) https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Wang, Ban Pan, Jichun Liu, Zhonghui Unraveling FOXO3a and USP18 Functions in Idiopathic Pulmonary Fibrosis through Single-Cell RNA Sequencing of Mouse and Human Lungs |
title | Unraveling FOXO3a and USP18 Functions in Idiopathic Pulmonary Fibrosis through Single-Cell RNA Sequencing of Mouse and Human Lungs |
title_full | Unraveling FOXO3a and USP18 Functions in Idiopathic Pulmonary Fibrosis through Single-Cell RNA Sequencing of Mouse and Human Lungs |
title_fullStr | Unraveling FOXO3a and USP18 Functions in Idiopathic Pulmonary Fibrosis through Single-Cell RNA Sequencing of Mouse and Human Lungs |
title_full_unstemmed | Unraveling FOXO3a and USP18 Functions in Idiopathic Pulmonary Fibrosis through Single-Cell RNA Sequencing of Mouse and Human Lungs |
title_short | Unraveling FOXO3a and USP18 Functions in Idiopathic Pulmonary Fibrosis through Single-Cell RNA Sequencing of Mouse and Human Lungs |
title_sort | unraveling foxo3a and usp18 functions in idiopathic pulmonary fibrosis through single-cell rna sequencing of mouse and human lungs |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651367/ https://www.ncbi.nlm.nih.gov/pubmed/38025194 http://dx.doi.org/10.1055/s-0043-1776697 |
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