Tacrolimus-binding protein FKBP8 directs myosin light chain kinase-dependent barrier regulation and is a potential therapeutic target in Crohn’s disease

• Published in: Gut Vol. 72; no. 5; pp. 870 - 881
• Main Authors: Zuo, Li, Kuo, Wei-Ting, Cao, Feng, Chanez-Paredes, Sandra D, Zeve, Daniel, Mannam, Prabhath, Jean-François, Léa, Day, Anne, Vallen Graham, W, Sweat, Yan Y, Shashikanth, Nitesh, Breault, David T, Turner, Jerrold R
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and British Society of Gastroenterology 01.05.2023; BMJ Publishing Group LTD
• Subjects: actin cytoskeleton; Animals; Biopsy; Caco-2 Cells; Cell junctions; Crohn Disease - drug therapy; Crohn Disease - metabolism; Crohn's disease; Epithelial cells; Humans; IBD basic research; Inflammatory bowel disease; Inflammatory bowel diseases; intestinal barrier function; Intestinal Mucosa - metabolism; intestinal stem cell; Intestine; Kinases; Light; Mice; Mice, Knockout; Myosin-light-chain kinase; Myosin-Light-Chain Kinase - metabolism; Organoids; Patients; Permeability; Phosphorylation; Protein interaction; Proteins; Recruitment; Remission (Medicine); Risk factors; Tacrolimus; Tacrolimus - pharmacology; Tacrolimus Binding Proteins - metabolism; Tacrolimus-binding protein; Therapeutic targets; Tight Junctions - physiology; TNF; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumors; Womens health; United States > US; Massachusetts; IBD basic research; actin cytoskeleton; intestinal stem cell; intestinal barrier function; TNF

ObjectiveIntestinal barrier loss is a Crohn’s disease (CD) risk factor. This may be related to increased expression and enzymatic activation of myosin light chain kinase 1 (MLCK1), which increases intestinal paracellular permeability and correlates with CD severity. Moreover, preclinical studies hav...