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Caveolin-1 siRNA Increases the Pulmonary Microvascular and Alveolar Epithelial Permeability in Rats.
MedLine Citation:
PMID:  20693910     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND: : Increased pulmonary microvascular and epithelial permeability are important contributors to pulmonary edema in acute lung injury. In this study, we used small interfering RNA (siRNA) to knock down caveolin-1 expression in rat lungs and to confirm the important role of caveolin-1 in regulating pulmonary edema.
METHOD: : After pulmonary injection of siRNA against caveolin-1 messenger RNA incorporated in liposomes with three concentrations of 0.4, 0.8, and 1.2 mg/kg, the gene silencing rate and the effects of caveolin-1 siRNA on aquaporin (AQP)-1, AQP-5, and epithelial sodium channel (ENaC) were detected. For pulmonary permeability analysis, Evans blue fluorimetry, ratios of albumin concentrations between blood and bronchoalveolar lavage, and wet/dry weight ratios were measured. The impacts of caveolin-1 suppression on interendothelial junctions were evaluated by the performance of electron microscopy and the analysis of vascular endothelial (VE)-cadherin Western blot. Alveolar wall thickness analysis and chest fluoroscopy were performed to determine the pulmonary edema degree.
RESULTS: : After 72 hours of injection, the gene silencing rate of caveolin-1 siRNA is about 87%. AQP-1, AQP-5, ENaC-α, ENaC-β, ENaC-γ, and VE-cadherin protein levels were decreased by 63%, 66%, 80%, 90%, 89%, and 50%, respectively. Caveolin-1 siRNA also resulted in increasing microvascular and epithelial permeability and pulmonary edema.
CONCLUSION: : These data suggest that caveolin-1 plays an important part in regulating the pulmonary permeability by modifying AQP-1, AQP-5, ENaC, and VE-cadherin.
Authors:
Chengjin Gao; Rongrong Li; Jingning Huan; Wei Li
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of trauma     Volume:  70     ISSN:  1529-8809     ISO Abbreviation:  J Trauma     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376373     Medline TA:  J Trauma     Country:  United States    
Other Details:
Languages:  eng     Pagination:  210-9     Citation Subset:  AIM; IM    
Affiliation:
From the Department of Burn and Plastic Surgery (C.G., J.H.), Rui Jin Hospital, Shanghai Jiao Tong University, School of Medicine; Division of Radiation-Oncology (R.L.), Oral and Maxillofacial Surgery Department, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; and Department of Burn and Plastic Surgery (W.L.), Jinshan Hospital, Fudan University, Shanghai, China.
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