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A model of the aged lung epithelium in idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF) is an age-related disorder that carries a universally poor prognosis and is thought to arise from repetitive micro injuries to the alveolar epithelium. To date, a major factor limiting our understanding of IPF is a deficiency of disease models, particularly in vit...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312437/ https://www.ncbi.nlm.nih.gov/pubmed/34238764 http://dx.doi.org/10.18632/aging.203291 |
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author | Shaghaghi, Hoora Cuevas-Mora, Karina Para, Rachel Tran, Cara Roque, Willy Robertson, Matthew J. Rosas, Ivan O. Summer, Ross Romero, Freddy |
author_facet | Shaghaghi, Hoora Cuevas-Mora, Karina Para, Rachel Tran, Cara Roque, Willy Robertson, Matthew J. Rosas, Ivan O. Summer, Ross Romero, Freddy |
author_sort | Shaghaghi, Hoora |
collection | PubMed |
description | Idiopathic pulmonary fibrosis (IPF) is an age-related disorder that carries a universally poor prognosis and is thought to arise from repetitive micro injuries to the alveolar epithelium. To date, a major factor limiting our understanding of IPF is a deficiency of disease models, particularly in vitro models that can recapitulate the full complement of molecular attributes in the human condition. In this study, we aimed to develop a model that more closely resembles the aberrant IPF lung epithelium. By exposing mouse alveolar epithelial cells to repeated, low doses of bleomycin, instead of usual one-time exposures, we uncovered changes strikingly similar to those in the IPF lung epithelium. This included the acquisition of multiple phenotypic and functional characteristics of senescent cells and the adoption of previously described changes in mitochondrial homeostasis, including alterations in redox balance, energy production and activity of the mitochondrial unfolded protein response. We also uncovered dramatic changes in cellular metabolism and detected a profound loss of proteostasis, as characterized by the accumulation of cytoplasmic protein aggregates, dysregulated expression of chaperone proteins and decreased activity of the ubiquitin proteasome system. In summary, we describe an in vitro model that closely resembles the aberrant lung epithelium in IPF. We propose that this simple yet powerful tool could help uncover new biological mechanisms and assist in developing new pharmacological tools to treat the disease. |
format | Online Article Text |
id | pubmed-8312437 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-83124372021-07-27 A model of the aged lung epithelium in idiopathic pulmonary fibrosis Shaghaghi, Hoora Cuevas-Mora, Karina Para, Rachel Tran, Cara Roque, Willy Robertson, Matthew J. Rosas, Ivan O. Summer, Ross Romero, Freddy Aging (Albany NY) Research Paper Idiopathic pulmonary fibrosis (IPF) is an age-related disorder that carries a universally poor prognosis and is thought to arise from repetitive micro injuries to the alveolar epithelium. To date, a major factor limiting our understanding of IPF is a deficiency of disease models, particularly in vitro models that can recapitulate the full complement of molecular attributes in the human condition. In this study, we aimed to develop a model that more closely resembles the aberrant IPF lung epithelium. By exposing mouse alveolar epithelial cells to repeated, low doses of bleomycin, instead of usual one-time exposures, we uncovered changes strikingly similar to those in the IPF lung epithelium. This included the acquisition of multiple phenotypic and functional characteristics of senescent cells and the adoption of previously described changes in mitochondrial homeostasis, including alterations in redox balance, energy production and activity of the mitochondrial unfolded protein response. We also uncovered dramatic changes in cellular metabolism and detected a profound loss of proteostasis, as characterized by the accumulation of cytoplasmic protein aggregates, dysregulated expression of chaperone proteins and decreased activity of the ubiquitin proteasome system. In summary, we describe an in vitro model that closely resembles the aberrant lung epithelium in IPF. We propose that this simple yet powerful tool could help uncover new biological mechanisms and assist in developing new pharmacological tools to treat the disease. Impact Journals 2021-07-08 /pmc/articles/PMC8312437/ /pubmed/34238764 http://dx.doi.org/10.18632/aging.203291 Text en Copyright: © 2021 Shaghaghi et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Shaghaghi, Hoora Cuevas-Mora, Karina Para, Rachel Tran, Cara Roque, Willy Robertson, Matthew J. Rosas, Ivan O. Summer, Ross Romero, Freddy A model of the aged lung epithelium in idiopathic pulmonary fibrosis |
title | A model of the aged lung epithelium in idiopathic pulmonary fibrosis |
title_full | A model of the aged lung epithelium in idiopathic pulmonary fibrosis |
title_fullStr | A model of the aged lung epithelium in idiopathic pulmonary fibrosis |
title_full_unstemmed | A model of the aged lung epithelium in idiopathic pulmonary fibrosis |
title_short | A model of the aged lung epithelium in idiopathic pulmonary fibrosis |
title_sort | model of the aged lung epithelium in idiopathic pulmonary fibrosis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312437/ https://www.ncbi.nlm.nih.gov/pubmed/34238764 http://dx.doi.org/10.18632/aging.203291 |
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