Chromogranin A regulates gut permeability via the antagonistic actions of its proteolytic peptides.

摘要: Aim A 'leaky' gut barrier has been implicated in the initiation and progression of a multitude diseases, e.g., inflammatory bowel disease (IBD), irritable syndrome, celiac disease. Here we show how pro-hormone Chromogranin (CgA), produced by enteroendocrine cells, Catestatin (CST: hCgA352-372 ), most abundant CgA-derived proteolytic peptide, affect barrier. Methods Colon tissues from region-specific CST-knockout (CST-KO) mice, CgA-knockout (CgA-KO) WT mice were analyzed immunohistochemistry, Western blot, ultrastructural flowcytometry studies. FITC-dextran assays used to measure intestinal function. Mice supplemented with CST or CgA fragment pancreastatin (PST: CgA250-301 ). The microbial composition cecum was determined. levels measured blood IBD patients. Results Plasma elevated CST-KO displayed (i) elongated tight, adherens junctions desmosomes similar patients, (ii) expression Claudin 2, (iii) inflammation. measurements showed increased paracellular permeability mice. This correlated higher ratio Firmicutes Bacteroidetes, dysbiotic pattern commonly encountered various diseases. Supplementation recombinant restored reversed inflammation, whereas supplementation and/or PST CgA-KO that is regulated antagonistic roles these two peptides: reduces increases permeability. Conclusion regulates both necessary sufficient reduce primarily acts antagonizing PST.