title: Microtubule-associated protein 1S-related autophagy inhibits apoptosis of intestinal epithelial cells via Wnt/β-catenin signaling in Crohn's disease.
abstract: Many autophagy-related genes, to our knowledge, have been identified as Crohn's disease (CD) polymorphic sites by genomic wide studies. As a novel member of the microtubule-associated protein 1 (MAP1) family, MAP1S is a microtubule-binding proteins involved in autophagy. However, its expression and potential functions in CD have not been understood. For the first time, we discovered the up-regulated MAP1S and autophagy level (indicated by LC3-Ⅱ/LC3-Ⅰ) in inflamed epithelium among CD patients. Similarly, in TNBS-induced murine colitis model, MAP1S expression was obviously increased. Meanwhile, we found the co-location of MAP1S and active-caspase 3 which acted as "apoptotic executor" which might indicate the basis of their co-efficient. At the cellular level, MAP1S silencing inhibited starvation-induced over-expression of active-caspase 3 partially via Wnt/β-catenin signaling activation in HCT-116 cells. Finally, we demonstrated that IWP-2, an inhibitor of the Wnt/β-catenin signaling, reversed the down-regulation of active-caspase 3 induced by MAP1S siRNA in HCT-116 cells. Taken together, our results suggested that MAP1S were up-regulated among CD patients and MAP1S-related autophagy inhibits apoptosis of intestinal epithelial cells (IECs) through Wnt/β-catenin signaling pathway which might play a vital role in the protection of intestinal mucosal barrier and inhibition the progression of CD.
authors.affiliation: The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Bai
authors.affiliation: Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Jian'an
authors.initials: J
authors.lastname: Bai
authors.affiliation: Binzhou Central Hospital, Binzhou, China.
authors.forename: Yanhai
authors.initials: Y
authors.lastname: Li
authors.affiliation: Binzhou Central Hospital, Binzhou, China.
authors.forename: Delong
authors.initials: D
authors.lastname: Tian
authors.affiliation: The First Affiliated Hospital with Nanjing Medical University, Nanjing, China. Electronic address: ruihuashi0628@163.com.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Shi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D052160:Benzothiazoles / Q000494:pharmacology; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D003424:Crohn Disease / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D014302:Trinitrobenzenesulfonic Acid; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology*
chemical_list: D052160:Benzothiazoles; C000611186:IWP-2 compound; C493240:MAP1S protein, human; C570460:MAP1S protein, mouse; D008869:Microtubule-Associated Proteins; D014302:Trinitrobenzenesulfonic Acid; D053148:Caspase 3
keywords: Apoptosis; Autophagy; Crohn's disease; MAP1S; Wnt/β-catenin