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Introduction
Ulcerative colitis (UC) is an important type of inflammatory bowel disease (IBD), which is a chronic non-specific autoimmune disease. Although environmental factors, infections and immunological and psychological factors can lead to the occurrence of the disease, the specific pathogenesis remains to be elucidated.
Intestinal mucosal barrier damage has been recognized as one of the key factors in the pathogenesis of IBD. A single layer of epithelial cells covering the intestinal mucosal surface, form a physical barrier to withstand external stimuli and infections and maintain homeostasis between the intestinal cavity and internal tissues (1,2). The function of intestinal mucosal barrier protection is often referred to as intestinal permeability in IBD (3). Hyperactivity and increased permeability of intestinal epithelium is an important characteristic of IBD (4). A previous study confirmed that colonic epithelial barrier dysfunction is considered to be important in the initiation of intestinal inflammation (5). The main functional characteristic of intestinal epithelial barrier dysfunction is intestinal permeability alterations, which not only easily lead to disease, but may also be an important reason for the onset of delayed healing (6,7).
Barrier function is dynamic and can be adjusted by a variety of physiological and pathophysiological stimuli (8). Several lines of evidence support the theory that myosin light chain kinase (MLCK)-dependent phosphorylation of MLC has a central role in the pathogenesis of IBD (9–11). The levels of MLCK are positively associated with disease severity in UC. Increased MLCK expression can lead to the destruction of tight junctions (TJs), which is associated with increased intestinal permeability (12). This phenomenon can be prevented by MLCK inhibitors (13).
Adrenomedullin (AM) is an endogenous vasoactive peptide, which is closely associated with cell metabolism, immune function and endocrine and cardiovascular function, and is important in a number of tissues and organs (14). Previous studies have suggested that intestinal epithelial cells may be an important target for the protective effect of AM. Sakata et al found that AM had a higher expression in the cecum and colon and may have an important protective role in the colon (15), however, the specific mechanisms involved remain to be elucidated. Prior studies have demonstrated that AM may exert a protective effect in the gut by its anti-inflammatory properties and by suppressing the generation of...