- Title
- Divergent roles for clusterin in lung injury and repair
- Creator
- Habiel, David M.; Camelo, Ana; Pilataxi, Fernanda; Clarke, Lori; Grant, Ethan; Lewis, Arthur; Moore, Bethany; Knight, Darryl A.; Hogaboam, Cory M.; Murray, Lynne A.; Espindola, Milena; Burwell, Timothy; Hanna, Richard; Miranda, Elena; Carruthers, Alan; Bell, Matthew; Coelho, Ana Lucia; Liu, Hao
- Relation
- NHMRC.1099569 http://purl.org/au-research/grants/nhmrc/1099569
- Relation
- Scientific Reports Vol. 7, no. 15444
- Publisher Link
- http://dx.doi.org/10.1038/s41598-017-15670-5
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2017
- 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.
- Subject
- experimental models of disease; respiratory tract diseases; senescence
- Identifier
- http://hdl.handle.net/1959.13/1353200
- Identifier
- uon:31071
- Identifier
- ISSN:2045-2322
- Rights
- 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/.
- Language
- eng
- Full Text
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