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Clusterin Deficiency Exacerbates Hyperoxia-Induced Acute Lung Injury

Authors
 Jung Yeon Hong  ;  Mi Na Kim  ;  Eun Gyul Kim  ;  Jae Woo Lee  ;  Hye Rin Kim  ;  Soo Yeon Kim  ;  Soon Min Lee  ;  Yoon Hee Kim  ;  Kyung Won Kim  ;  Myung Hyun Sohn 
Citation
 CELLS, Vol.10(4) : 944, 2021-04 
Journal Title
 CELLS 
ISSN
 2073-4409 
Issue Date
2021-04
Keywords
acute lung injury ; apoptosis ; clusterin ; hyperoxia ; inflammation
Abstract
Exposure to high oxygen concentrations leads to generation of excessive reactive oxygen species, causing cellular injury and multiple organ dysfunctions and is associated with a high mortality rate. Clusterin (CLU) is a heterodimeric glycoprotein that mediates several intracellular signaling pathways, including cell death and inflammation. However, the role of CLU in the pathogenesis of hyperoxic acute lung injury (HALI) is unknown. Wild-type (WT) and CLU-deficient mice and cultured human airway epithelial cells were used. Changes in cell death- and inflammation-related molecules with or without hyperoxia exposure in cells and animals were determined. Hyperoxia induced an increase in CLU expression in mouse lungs and human airway epithelial cells. Mice lacking CLU had increased HALI and mortality rate compared with WT mice. In vitro, CLU-disrupted cells showed enhanced release of cytochrome c, Bax translocation, cell death and inflammatory cytokine expression. However, treatment with recombinant CLU attenuated hyperoxia-induced apoptosis. Moreover, the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed metabolic pathways, hematopoietic cell lineage, response to stress and localization and regulation of immune system that were differentially regulated between WT and CLU-/- mice. These results demonstrate that prolonged hyperoxia-induced lung injury is associated with CLU expression and that CLU replenishment may alleviate hyperoxia-induced cell death.
Files in This Item:
T202101647.pdf Download
DOI
10.3390/cells10040944
Appears in Collections:
1. College of Medicine (의과대학) > Others (기타) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Won(김경원) ORCID logo https://orcid.org/0000-0003-4529-6135
Kim, Mina(김미나) ORCID logo https://orcid.org/0000-0002-1675-0688
Kim, Soo Yeon(김수연) ORCID logo https://orcid.org/0000-0003-4965-6193
Kim, Yoon Hee(김윤희) ORCID logo https://orcid.org/0000-0002-2149-8501
Sohn, Myung Hyun(손명현) ORCID logo https://orcid.org/0000-0002-2478-487X
Lee, Soon Min(이순민) ORCID logo https://orcid.org/0000-0003-0174-1065
Hong, Jung Yeon(홍정연) ORCID logo https://orcid.org/0000-0003-0406-9956
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182956
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