title: MicroRNA-124 Promotes Intestinal Inflammation by Targeting Aryl Hydrocarbon Receptor in Crohn's Disease.
abstract: OBJECTIVE
  Dysregulation of microRNAs (miRNAs) is associated with a variety of diseases, including Crohn's disease (CD), but the essential biological functions and crucial targets of miRNAs remain largely unknown. The present study investigated the aberrant colonic mucosal miRNAs in active CD patients.
  
  
  METHODS
  miRNA levels were assayed in inflamed colon of active CD patients by quantitative real-time polymerase chain reaction. The influence of differential expressed miR-124 on its putative target, the aryl hydrocarbon receptor (AHR), was investigated in CD patients, intestinal epithelial cells (IECs) and 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis mice. The role of miR-124 was further studied in experimental colitis mice by intracolonic administration of miR-124 inhibitors or precursors.
  
  
  RESULTS
  We found an inverse correlation between miR-124 and AHR protein levels in colon tissues and IECs of active CD patients. Further results demonstrated that miR-124 suppressed AHR expression by directly targeting the AHR 3'-untranslated region (3'-UTR) in Caco-2 cells and HT-29 cells. MiR-124 mediated the inflammatory response in lipopolysaccharide-stimulated cells through retroregulation of AHR in vitro. Downregulation or upregulation of miR-124 in TNBS-induced colitic colon alleviated or aggravated experimental colitis, respectively.
  
  
  CONCLUSIONS
  These findings suggest that miR-124 induces intestinal inflammation by inhibiting AHR to modulate pro-inflammatory cytokine production and thereby promotes the pathogenesis of CD.
authors.affiliation: Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu Province, PR China Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Zhongda Hospital, Southeast University, Nanjing, Jiangsu Province, PR China Department of Cardiovascular Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China.
authors.forename: Teng
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Gastroenterology, Xuzhou Central Hospital, Xuzhou, Jiangsu Province, PR China Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China.
authors.forename: Weixu
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu Province, PR China Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu Province, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu Province, PR China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Gastroenterology, Nanjing General Hospital of Nanjing Military Command, Nanjing, Jiangsu Province, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China.
authors.forename: Risheng
authors.initials: R
authors.lastname: Cao
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu Province, PR China ruihuashi@126.com.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Shi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D018938:Caco-2 Cells; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D014302:Trinitrobenzenesulfonic Acid; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D016207:Cytokines; D035683:MicroRNAs; D018336:Receptors, Aryl Hydrocarbon; D014302:Trinitrobenzenesulfonic Acid; C111235:AHR protein, human; C484722:Ahr protein, mouse; C509207:MIRN124 microRNA, human; C540079:Mirn124 microRNA, mouse
keywords: Crohn’s disease; aryl hydrocarbon receptor; intestinal epithelial cell; miR-124