https://scholars.lib.ntu.edu.tw/handle/123456789/565666
標題: | SHANK3 Regulates Intestinal Barrier Function Through Modulating ZO-1 Expression Through the PKCϵ-dependent Pathway | 作者: | SHU-CHEN WEI Yang-Yen, H.-F. PO-NIEN TSAO Weng, M.-T. CHIEN-CHIH TUNG LINDA CHIA-HUI YU LIANG-CHUAN LAI Hsiao, J.-H. Chuang, E.Y. CHIA-TUNG SHUN YEN-HSUAN NI Xavier, R.J. Podolsky, D.K. Yen, J.J.Y. ERIC YAO-YU CHUANG |
公開日期: | 2017 | 出版社: | Lippincott Williams and Wilkins | 卷: | 23 | 期: | 10 | 起(迄)頁: | 1730-1740 | 來源出版物: | Inflammatory Bowel Diseases | 摘要: | Background: The integrity of the gut barrier in patients with inflammatory bowel disease is known to be impaired but the exact mechanisms remain mostly unknown. SHANK3 mutations are associated with autism, and patients with autism are known to have higher proportions of inflammatory bowel disease. Here, we explore the role of SHANK3 in inflammatory bowel disease, both in vivo and in vitro. Methods: Dextran sulfate sodium colitis was induced in SHANK3 knockout mice. Transepithelial electrical resistance, paracellular permeability, and Salmonella invasion assays were used to evaluate epithelial barrier function, in vitro and in vivo. Expression of tight junction proteins, protein kinases, and MAP kinase phosphorylation changes were analyzed by immunoblotting after overexpression or knockdown of SHANK3 expression. SHANK3 expression in intestinal tissue from patients with Crohn's disease was analyzed by quantitative polymerase chain reaction and immunohistochemistry. Results: SHANK3 knockout mice were more susceptible to dextran sulfate sodium. SHANK3 knockout resulted in a leaky epithelial barrier phenotype, as demonstrated by decreased transepithelial electrical resistance, increased paracellular permeability, and increased Salmonella invasion. Overexpression of SHANK3 enhanced ZO-1 expression, and knockdown of SHANK3 resulted in decreased expression of ZO-1. Regulation of ZO-1 expression by SHANK3 seems to be mediated through a PKC?-dependent pathway. SHANK3 expression correlated with ZO-1 and PKC? in colonic tissue of patients with Crohn's disease. Conclusions: The expression level of SHANK3 affects ZO-1 expression and the barrier function in intestinal epithelial cells. This may provide novel insights in Crohn's disease pathogenesis and treatment. ? Copyright 2017 Crohn's & Colitis Foundation. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85029758336&doi=10.1097%2fMIB.0000000000001250&partnerID=40&md5=c0b851bbfc7515ce23f83a64a5586197 https://scholars.lib.ntu.edu.tw/handle/123456789/565666 |
ISSN: | 1078-0998 | DOI: | 10.1097/MIB.0000000000001250 | SDG/關鍵字: | claudin 4; fluorescein isothiocyanate; glyceraldehyde 3 phosphate dehydrogenase; junctional adhesion molecule A; occludin; protein kinase C epsilon; protein SH3; protein ZO1; SH3 and multiple ankyrin repeat domains 3; small interfering RNA; unclassified drug; uvomorulin; dextran sulfate; nerve protein; protein kinase C epsilon; protein ZO1; SHANK3 protein, human; Shank3 protein, mouse; TJP1 protein, human; Tjp1 protein, mouse; animal experiment; animal model; animal tissue; Article; body weight; cell invasion assay; cell membrane permeability; confocal microscopy; controlled study; Crohn disease; densitometry; dextran sulfate sodium-induced colitis; electric resistance; flux assay; gene expression; gene overexpression; histology; human; human cell; immunoblotting; immunohistochemistry; intestine mucosa permeability; male; mouse; nonhuman; phenotype; priority journal; protein expression; real time polymerase chain reaction; reverse transcription polymerase chain reaction; RNA extraction; Salmonella enterica serovar Typhimurium; signal transduction; transepithelial resistance; Western blotting; animal; Caco-2 cell line; chemically induced; colitis; colon; disease model; epithelium cell; genetics; HCT 116 cell line; knockout mouse; MAPK signaling; metabolism; pathology; phosphorylation; Salmonella; Animals; Caco-2 Cells; Cell Membrane Permeability; Colitis; Colon; Crohn Disease; Dextran Sulfate; Disease Models, Animal; Epithelial Cells; HCT116 Cells; Humans; Male; MAP Kinase Signaling System; Mice; Mice, Knockout; Nerve Tissue Proteins; Phosphorylation; Protein Kinase C-epsilon; Salmonella; Zonula Occludens-1 Protein |
顯示於: | 醫學系 |
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