期刊
DIGESTIVE DISEASES AND SCIENCES
卷 64, 期 2, 页码 421-431出版社
SPRINGER
DOI: 10.1007/s10620-018-5246-6
关键词
Mucosal protection; Osteopontin; Occludin; Tight junction
资金
- Research Institute of Veterinary Science, College of Veterinary Medicine, Seoul National University
- Korea Mouse Phenotyping Project of a National Research Foundation - Korean government (MSIP) [NRF-2016M3A9D5A01952416]
BackgroundOsteopontin (OPN) has been reported to play an important role in intestinal mucosal protection. Although OPN may have positive effects on tight junctions, the exact relationship between OPN and tight junctions has yet to be elucidated.AimsTo investigate the role of OPN on tight junctions.MethodsWe evaluated clinical signs and histopathology of acute colitis induced by dextran sodium sulfate (DSS) in OPN knockout and wild-type (WT) mice in vivo. Expression levels of occludin and zonula occludens-1 were examined using immunofluorescence. For in vitro analysis, an siRNA-mediated OPN-suppressed Caco-2 monolayer was used. Expression levels and patterns of occludin were analyzed by immunofluorescence, and transepithelial electrical resistance (TER) was measured to evaluate barrier function. Triton X-100 fractionation was used to analyze phosphorylated occludin associated with tight junctional localization.ResultsOPN deficiency resulted in an elevated disease activity index, shortened colon length, and aggravated histological signs in mice with DSS-induced acute colitis compared to WT mice. OPN deficiency decreased occludin expression in the colonic mucosa. In Caco-2 monolayers, OPN suppression reduced junctional occludin and redistributed it into the intracellular compartment with decreased TER. Furthermore, western blot for occludin from Triton X-100 insoluble fraction revealed that OPN suppression reduced the phosphorylated form of occludin, which is actually distributed in the tight junction.ConclusionsOur study showed that OPN is essential for maintaining the tight junction complex by allowing occludin to localize at tight junctions. This could constitute additional evidence that OPN plays a crucial role in intestinal mucosal protection.
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