PMID- 20558631
OWN - NLM
STAT- MEDLINE
DCOM- 20101021
LR  - 20211020
IS  - 1535-4970 (Electronic)
IS  - 1073-449X (Print)
IS  - 1073-449X (Linking)
VI  - 182
IP  - 7
DP  - 2010 Oct 1
TI  - The chitinase-like proteins breast regression protein-39 and YKL-40 regulate 
      hyperoxia-induced acute lung injury.
PG  - 918-28
LID - 10.1164/rccm.200912-1793OC [doi]
AB  - 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.
FAU - Sohn, Myung Hyun
AU  - Sohn MH
AD  - Department of Pediatrics, and Institute of Allergy, Severance Biomedical Science 
      Institute, BK21 Project for Medical Science, Yonsei University College of 
      Medicine, Seoul, Korea.
FAU - Kang, Min-Jong
AU  - Kang MJ
FAU - Matsuura, Hiroshi
AU  - Matsuura H
FAU - Bhandari, Vineet
AU  - Bhandari V
FAU - Chen, Ning-Yuan
AU  - Chen NY
FAU - Lee, Chun Geun
AU  - Lee CG
FAU - Elias, Jack A
AU  - Elias JA
LA  - eng
GR  - R0-HL-064242/HL/NHLBI NIH HHS/United States
GR  - R0-HL-081639/HL/NHLBI NIH HHS/United States
GR  - R0-HL-084225/HL/NHLBI NIH HHS/United States
GR  - R0-HL-093017/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100617
PL  - United States
TA  - Am J Respir Crit Care Med
JT  - American journal of respiratory and critical care medicine
JID - 9421642
RN  - 0 (Adipokines)
RN  - 0 (CHI3L1 protein, human)
RN  - 0 (Chil1 protein, mouse)
RN  - 0 (Chitinase-3-Like Protein 1)
RN  - 0 (Glycoproteins)
RN  - 0 (Lectins)
SB  - IM
MH  - Acute Lung Injury/*physiopathology
MH  - Adipokines
MH  - Animals
MH  - Apoptosis
MH  - Bronchopulmonary Dysplasia/*physiopathology
MH  - Cells, Cultured
MH  - Chitinase-3-Like Protein 1
MH  - Female
MH  - Glycoproteins/*metabolism
MH  - Humans
MH  - Hyperoxia/*physiopathology
MH  - Infant, Newborn
MH  - *Infant, Premature
MH  - Inflammation
MH  - Lectins/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Respiratory Mucosa/metabolism
MH  - Survival Analysis
PMC - PMC2970863
EDAT- 2010/06/19 06:00
MHDA- 2010/10/22 06:00
PMCR- 2011/10/01
CRDT- 2010/06/19 06:00
PHST- 2010/06/19 06:00 [entrez]
PHST- 2010/06/19 06:00 [pubmed]
PHST- 2010/10/22 06:00 [medline]
PHST- 2011/10/01 00:00 [pmc-release]
AID - 200912-1793OC [pii]
AID - ajrccm1827918 [pii]
AID - 10.1164/rccm.200912-1793OC [doi]
PST - ppublish
SO  - Am J Respir Crit Care Med. 2010 Oct 1;182(7):918-28. doi: 
      10.1164/rccm.200912-1793OC. Epub 2010 Jun 17.