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The chitinase-like proteins breast regression protein-39 and YKL-40 regulate hyperoxia-induced acute lung injury.

Authors
 Myung Hyun Sohn  ;  Min-Jong Kang  ;  Hiroshi Matsuura  ;  Vineet Bhandari  ;  Ning-Yuan Chen  ;  Chun Geun Lee  ;  Jack A. Elias 
Citation
 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol.182(7) : 918-928, 2010 
Journal Title
 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 
ISSN
 1073-449X 
Issue Date
2010
MeSH
Acute Lung Injury/physiopathology* ; Adipokines ; Animals ; Apoptosis ; Bronchopulmonary Dysplasia/physiopathology* ; Cells, Cultured ; Chitinase-3-Like Protein 1 ; Female ; Glycoproteins/metabolism* ; Humans ; Hyperoxia/physiopathology* ; Infant, Newborn ; Infant, Premature* ; Inflammation ; Lectins/metabolism* ; Male ; Mice ; Mice, Transgenic ; Respiratory Mucosa/metabolism ; Survival Analysis
Keywords
BRP-39 ; YKL-40 ; hyperoxygen ; BPD ; HALI
Abstract
RATIONALE: Prolonged exposure to 100% O(2) causes hyperoxic acute lung injury (HALI), characterized by alveolar epithelial cell injury and death. We previously demonstrated that the murine chitinase-like protein, breast regression protein (BRP)-39 and its human homolog, YKL-40, inhibit cellular apoptosis. However, the regulation and roles of these molecules in hyperoxia have not been addressed. OBJECTIVES: We hypothesized that BRP-39 and YKL-40 (also called chitinase-3-like 1) play important roles in the pathogenesis of HALI. METHODS: We characterized the regulation of BRP-39 during HALI and the responses induced by hyperoxia in wild-type mice, BRP-39-null (-/-) mice, and BRP-39(-/-) mice in which YKL-40 was overexpressed in respiratory epithelium. We also compared the levels of tracheal aspirate YKL-40 in premature newborns with respiratory failure. MEASUREMENTS AND MAIN RESULTS: These studies demonstrate that hyperoxia inhibits BRP-39 in vivo in the murine lung and in vitro in epithelial cells. They also demonstrate that BRP-39(-/-) mice have exaggerated permeability, protein leak, oxidation, inflammatory, chemokine, and epithelial apoptosis responses, and experience premature death in 100% O(2). Lastly, they demonstrate that YKL-40 ameliorates HALI, prolongs survival in 100% O(2), and rescues the exaggerated injury response in BRP-39(-/-) animals. In accord with these findings, the levels of tracheal aspirate YKL-40 were lower in premature infants treated with hyperoxia for respiratory failure who subsequently experienced bronchopulmonary dysplasia or death compared with those that did not experience these complications. CONCLUSIONS: These studies demonstrate that hyperoxia inhibits BRP-39/YKL-40, and that BRP-39 and YKL-40 are critical regulators of oxidant injury, inflammation, and epithelial apoptosis in the murine and human lung
Files in This Item:
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DOI
10.1164/rccm.200912-1793OC
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Sohn, Myung Hyun(손명현) ORCID logo https://orcid.org/0000-0002-2478-487X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/102337
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