Clusterin Deficiency Exacerbates Hyperoxia-Induced Acute Lung Injury
Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine,134 Sinchon-Dong, Seoul 03722, Korea
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Author to whom correspondence should be addressed.
Academic Editors: Stijn De Langhe and Alexander E. Kalyuzhny
Cells 2021, 10(4), 944; https://doi.org/10.3390/cells10040944
Received: 8 February 2021
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Revised: 7 April 2021
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Accepted: 16 April 2021
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Published: 19 April 2021
(This article belongs to the Section Cell Signaling)
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.
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Keywords:
clusterin; acute lung injury; hyperoxia; apoptosis; inflammation
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MDPI and ACS Style
Hong, J.Y.; Kim, M.N.; Kim, E.G.; Lee, J.W.; Kim, H.R.; Kim, S.Y.; Lee, S.M.; Kim, Y.H.; Kim, K.W.; Sohn, M.H. Clusterin Deficiency Exacerbates Hyperoxia-Induced Acute Lung Injury. Cells 2021, 10, 944. https://doi.org/10.3390/cells10040944
AMA Style
Hong JY, Kim MN, Kim EG, Lee JW, Kim HR, Kim SY, Lee SM, Kim YH, Kim KW, Sohn MH. Clusterin Deficiency Exacerbates Hyperoxia-Induced Acute Lung Injury. Cells. 2021; 10(4):944. https://doi.org/10.3390/cells10040944
Chicago/Turabian StyleHong, Jung Y., Mi N. Kim, Eun G. Kim, Jae W. Lee, Hye R. Kim, Soo Y. Kim, Soon M. Lee, Yoon H. Kim, Kyung W. Kim, and Myung H. Sohn. 2021. "Clusterin Deficiency Exacerbates Hyperoxia-Induced Acute Lung Injury" Cells 10, no. 4: 944. https://doi.org/10.3390/cells10040944
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