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Divergent roles for Clusterin in Lung Injury and Repair

Lung fibrosis is an unabated wound healing response characterized by the loss and aberrant function of lung epithelial cells. Herein, we report that extracellular Clusterin promoted epithelial cell apoptosis whereas intracellular Clusterin maintained epithelium viability during lung repair. Unlike n...

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Autores principales: Habiel, David M., Camelo, Ana, Espindola, Milena, Burwell, Timothy, Hanna, Richard, Miranda, Elena, Carruthers, Alan, Bell, Matthew, Coelho, Ana Lucia, Liu, Hao, Pilataxi, Fernanda, Clarke, Lori, Grant, Ethan, Lewis, Arthur, Moore, Bethany, Knight, Darryl A., Hogaboam, Cory M., Murray, Lynne A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684342/
https://www.ncbi.nlm.nih.gov/pubmed/29133960
http://dx.doi.org/10.1038/s41598-017-15670-5
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author Habiel, David M.
Camelo, Ana
Espindola, Milena
Burwell, Timothy
Hanna, Richard
Miranda, Elena
Carruthers, Alan
Bell, Matthew
Coelho, Ana Lucia
Liu, Hao
Pilataxi, Fernanda
Clarke, Lori
Grant, Ethan
Lewis, Arthur
Moore, Bethany
Knight, Darryl A.
Hogaboam, Cory M.
Murray, Lynne A.
author_facet Habiel, David M.
Camelo, Ana
Espindola, Milena
Burwell, Timothy
Hanna, Richard
Miranda, Elena
Carruthers, Alan
Bell, Matthew
Coelho, Ana Lucia
Liu, Hao
Pilataxi, Fernanda
Clarke, Lori
Grant, Ethan
Lewis, Arthur
Moore, Bethany
Knight, Darryl A.
Hogaboam, Cory M.
Murray, Lynne A.
author_sort Habiel, David M.
collection PubMed
description Lung fibrosis is an unabated wound healing response characterized by the loss and aberrant function of lung epithelial cells. Herein, we report that extracellular Clusterin promoted epithelial cell apoptosis whereas intracellular Clusterin maintained epithelium viability during lung repair. Unlike normal and COPD lungs, IPF lungs were characterized by significantly increased extracellular Clusterin whereas the inverse was evident for intracellular Clusterin. In vitro and in vivo studies demonstrated that extracellular Clusterin promoted epithelial cell apoptosis while intercellular Clusterin modulated the expression of the DNA repair proteins, MSH2, MSH6, OGG1 and BRCA1. The fibrotic response in Clusterin deficient (CLU−/−) mice persisted after bleomycin and it was associated with increased DNA damage, reduced DNA repair responses, and elevated cellular senescence. Remarkably, this pattern mirrored that observed in IPF lung tissues. Together, our results show that cellular localization of Clusterin leads to divergent effects on epithelial cell regeneration and lung repair during fibrosis.
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spelling pubmed-56843422017-11-21 Divergent roles for Clusterin in Lung Injury and Repair Habiel, David M. Camelo, Ana Espindola, Milena Burwell, Timothy Hanna, Richard Miranda, Elena Carruthers, Alan Bell, Matthew Coelho, Ana Lucia Liu, Hao Pilataxi, Fernanda Clarke, Lori Grant, Ethan Lewis, Arthur Moore, Bethany Knight, Darryl A. Hogaboam, Cory M. Murray, Lynne A. Sci Rep Article Lung fibrosis is an unabated wound healing response characterized by the loss and aberrant function of lung epithelial cells. Herein, we report that extracellular Clusterin promoted epithelial cell apoptosis whereas intracellular Clusterin maintained epithelium viability during lung repair. Unlike normal and COPD lungs, IPF lungs were characterized by significantly increased extracellular Clusterin whereas the inverse was evident for intracellular Clusterin. In vitro and in vivo studies demonstrated that extracellular Clusterin promoted epithelial cell apoptosis while intercellular Clusterin modulated the expression of the DNA repair proteins, MSH2, MSH6, OGG1 and BRCA1. The fibrotic response in Clusterin deficient (CLU−/−) mice persisted after bleomycin and it was associated with increased DNA damage, reduced DNA repair responses, and elevated cellular senescence. Remarkably, this pattern mirrored that observed in IPF lung tissues. Together, our results show that cellular localization of Clusterin leads to divergent effects on epithelial cell regeneration and lung repair during fibrosis. Nature Publishing Group UK 2017-11-13 /pmc/articles/PMC5684342/ /pubmed/29133960 http://dx.doi.org/10.1038/s41598-017-15670-5 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Habiel, David M.
Camelo, Ana
Espindola, Milena
Burwell, Timothy
Hanna, Richard
Miranda, Elena
Carruthers, Alan
Bell, Matthew
Coelho, Ana Lucia
Liu, Hao
Pilataxi, Fernanda
Clarke, Lori
Grant, Ethan
Lewis, Arthur
Moore, Bethany
Knight, Darryl A.
Hogaboam, Cory M.
Murray, Lynne A.
Divergent roles for Clusterin in Lung Injury and Repair
title Divergent roles for Clusterin in Lung Injury and Repair
title_full Divergent roles for Clusterin in Lung Injury and Repair
title_fullStr Divergent roles for Clusterin in Lung Injury and Repair
title_full_unstemmed Divergent roles for Clusterin in Lung Injury and Repair
title_short Divergent roles for Clusterin in Lung Injury and Repair
title_sort divergent roles for clusterin in lung injury and repair
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684342/
https://www.ncbi.nlm.nih.gov/pubmed/29133960
http://dx.doi.org/10.1038/s41598-017-15670-5
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