The loss of αSNAP downregulates the expression of occludin in the intestinal epithelial cell of acute pancreatitis model |
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| Institution: | 1. Departamento de Fisiología y Bioquímica de la Nutrición Animal (INAN), Estación Experimental del Zaidín (CSIC), Armilla, Granada, Spain;2. Departamento de Nutrición y Bromatología, Facultad de Farmacia, Universidad de Granada, Granada, Spain;1. School of Biology, Miall Building, University of Leeds, Leeds LS2 9JT, UK;2. Leeds Institute of Biomedical and Clinical Sciences, St James''s University Hospital, University of Leeds, Leeds LS9 7TF, UK;3. Institute of Production, Disease and Welfare, University of Glasgow, Glasgow G61 1QH, UK;4. Environment and Life Sciences, University of Salford, Salford M5 4WT, UK;1. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510085, China;2. School of Informatics, Guangdong University of Foreign Studies, Guangzhou 510006, China;3. School of Fundamental Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China;4. School of Computer Science, South China Normal University, Guangzhou 510631, China |
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| Abstract: | Background and objectiveIntestinal barrier damage is an important event during the occurrence and progression of severe acute pancreatitis. The expression of occludin, one of the main components of the intestinal barrier proteins, is regulated by various factors related to intestinal barrier formation and the remodeling process. The αSNAP, as a novel membrane protein, is ubiquitously expressed in intestinal epithelial cells. This study aimed to investigate the role of αSNAP in acute pancreatitis and the relationship between occludin and αSNAP.MethodsMild and severe acute pancreatitis models were established by retrograde injections of 0.5% and 3.8% sodium taurocholate solutions, respectively, into rat pancreaticobiliary ducts. The animals were killed at 1, 2, and 3 days after the injection, and the pathological changes of the pancreas and intestinal mucosa, the changes in intestinal permeability, and the protein expression of occludin and αSNAP were assessed. Cultured epithelial IEC-6 cells were further infected with lentiviral αSNAP shRNA, cell apoptosis was determined with flow cytometry (FCM), and any changes in occludin expression were detected by Western blotting and immunofluorescent staining.ResultsThis pathologic study of a rat acute pancreatitis model indicated pancreatic tissue necrosis and inflammatory cell infiltration; the intestinal villi in the severe acute pancreatitis (SAP) group demonstrated edema, lodging, atrophy, and intestinal epithelial cell necrosis, and shedding. The intestinal permeability in rats with pancreatitis increased significantly. The SAP group showed significantly increased levels of serum TNF-α and endotoxins. The results of immunofluorescent staining and Western blotting revealed that compared with the SO (sham operation) and MAP (mild acute pancreatitis) groups, the SAP group displayed significantly downregulated protein expressions of αSNAP and occludin in the intestinal epithelial cells. After the lentiviral transduction of αSNAP shRNA, apoptosis in IEC-6 cells was drastically increased, whereas the expression of occludin was decreased significantly.ConclusionThe downregulated expression of αSNAP in intestinal epithelial cells leads to reduced occludin expression and enhanced apoptosis of intestinal epithelial cells. Hence, the permeability of the intestinal barrier may be increased in a severe acute pancreatitis model. |
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| Keywords: | Acute pancreatitis Intestinal barrier Rat αSNAP Occludin Tight junction |
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