PMID- 22559818
OWN - NLM
STAT- MEDLINE
DCOM- 20130610
LR  - 20211021
IS  - 1465-993X (Electronic)
IS  - 1465-9921 (Print)
IS  - 1465-9921 (Linking)
VI  - 13
IP  - 1
DP  - 2012 May 4
TI  - Hyperoxia disrupts pulmonary epithelial barrier in newborn rats via the 
      deterioration of occludin and ZO-1.
PG  - 36
LID - 10.1186/1465-9921-13-36 [doi]
AB  - BACKGROUND: Prolonged exposure to hyperoxia in neonates can cause hyperoxic acute 
      lung injury (HALI), which is characterized by increased pulmonary permeability 
      and diffuse infiltration of various inflammatory cells. Disruption of the 
      epithelial barrier may lead to altered pulmonary permeability and maintenance of 
      barrier properties requires intact epithelial tight junctions (TJs). However, in 
      neonatal animals, relatively little is known about how the TJ proteins are 
      expressed in the pulmonary epithelium, including whether expression of TJ 
      proteins is regulated in response to hyperoxia exposure. This study determines 
      whether changes in tight junctions play an important role in disruption of the 
      pulmonary epithelial barrier during hyperoxic acute lung injury. METHODS: Newborn 
      rats, randomly divided into two groups, were exposed to hyperoxia (95% oxygen) or 
      normoxia for 1-7 days, and the severity of lung injury was assessed; location and 
      expression of key tight junction protein occludin and ZO-1 were examined by 
      immunofluorescence staining and immunobloting; messenger RNA in lung tissue was 
      studied by RT-PCR; transmission electron microscopy study was performed for the 
      detection of tight junction morphology. RESULTS: We found that different 
      durations of hyperoxia exposure caused different degrees of lung injury in 
      newborn rats. Treatment with hyperoxia for prolonged duration contributed to more 
      serious lung injury, which was characterized by increased wet-to-dry ratio, 
      extravascular lung water content, and bronchoalveolar lavage fluid (BALF):serum 
      FD4 ratio. Transmission electron microscopy study demonstrated that hyperoxia 
      destroyed the structure of tight junctions and prolonged hyperoxia exposure, 
      enhancing the structure destruction. The results were compatible with 
      pathohistologic findings. We found that hyperoxia markedly disrupted the membrane 
      localization and downregulated the cytoplasm expression of the key tight junction 
      proteins occludin and ZO-1 in the alveolar epithelium by immunofluorescence. The 
      changes of messenger RNA and protein expression of occludin and ZO-1 in lung 
      tissue detected by RT-PCR and immunoblotting were consistent with the degree of 
      lung injury. CONCLUSIONS: These data suggest that the disruption of the pulmonary 
      epithelial barrier induced by hyperoxia is, at least in part, due to massive 
      deterioration in the expression and localization of key TJ proteins.
FAU - You, Kai
AU  - You K
AD  - Department of Pediatrics, Shengjing Hospital of China Medical University, 
      Shenyang 110004, China.
FAU - Xu, Xuewen
AU  - Xu X
FAU - Fu, Jianhua
AU  - Fu J
FAU - Xu, Shuyan
AU  - Xu S
FAU - Yue, Xiaohong
AU  - Yue X
FAU - Yu, Zhiling
AU  - Yu Z
FAU - Xue, Xindong
AU  - Xue X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120504
PL  - England
TA  - Respir Res
JT  - Respiratory research
JID - 101090633
RN  - 0 (Occludin)
RN  - 0 (Ocln protein, rat)
RN  - 0 (Tjp1 protein, rat)
RN  - 0 (Zonula Occludens-1 Protein)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Female
MH  - Hyperoxia/*metabolism/pathology
MH  - Occludin/*biosynthesis
MH  - Pregnancy
MH  - Pulmonary Alveoli/*metabolism/pathology
MH  - Random Allocation
MH  - Rats
MH  - Rats, Wistar
MH  - Respiratory Mucosa/*metabolism/pathology
MH  - Tight Junctions/metabolism/pathology
MH  - Zonula Occludens-1 Protein/*biosynthesis
PMC - PMC3424121
EDAT- 2012/05/09 06:00
MHDA- 2013/06/12 06:00
PMCR- 2012/05/04
CRDT- 2012/05/08 06:00
PHST- 2012/02/03 00:00 [received]
PHST- 2012/05/04 00:00 [accepted]
PHST- 2012/05/08 06:00 [entrez]
PHST- 2012/05/09 06:00 [pubmed]
PHST- 2013/06/12 06:00 [medline]
PHST- 2012/05/04 00:00 [pmc-release]
AID - 1465-9921-13-36 [pii]
AID - 10.1186/1465-9921-13-36 [doi]
PST - epublish
SO  - Respir Res. 2012 May 4;13(1):36. doi: 10.1186/1465-9921-13-36.