Caveolin-1 siRNA Increases the Pulmonary Microvascular and Alveolar Epithelial Permeability in Rats
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 caveolin1 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)-l, 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 (he 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％. AQP1, 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.
caveolae, aquaporins pulmonary edema alveolar wall wet to dry ratio.
Chengjin Gao Rongrong Li Jingning Huan Wei Li
Department of Burn and Plastic Surgery , Rui Jin Hospital, Shanghai Jiao Tong University, School of Division of Radiation-Oncology, Oral and Maxillofacial Surgery Department, Ninth Peoples Hospital A Department of Burn and Plastic Surgery. Jinshan Hospital, Fudan University, Shanghai, China
国际会议
上海
英文
113-122
2011-12-28（万方平台首次上网日期，不代表论文的发表时间）