title: Mobilization of epithelial mesenchymal transition genes distinguishes active from inactive lesional tissue in patients with ulcerative colitis.
abstract: Ulcerative colitis (UC) is a chronic, relapsing and debilitating idiopathic inflammation, with variable and complex pathophysiologies. Our objective was to elucidate patterns of gene expression underlying the progression of UC disease. Single endoscopic pinch FFPE biopsies (n = 41) were sampled at both active and inactive stages at the same site in individual UC patients and compared with each other and with non-inflammatory bowel disease healthy controls. Gene expression results were validated by quantitative reverse transcriptase-PCR (QRT-PCR), and results at the protein level were validated by immunohistochemistry and western blot. Analysis of microarray results demonstrated that UC patients in remission display an intermediate gene expression phenotype between active UC patients and controls. It is clear that UC active site recovery does not revert fully back to a healthy control phenotype. Both UC active and inactive tissue displayed evidence, at both the gene expression and protein level, of a positive precancerous state as indicated by increases in the expression of Chitinase 3-Like-1, and the colorectal cancer metastasis marker MMP1. A key distinguishing feature between active and inactive UC, however, was the mobilization of marker genes and proteins for the Epithelial Mesenchymal Transition (EMT) pathway only in active UC. Analysis of the gene expression signatures associated with UC remission identified multiple pathways which appear to be permanently dysregulated in UC patients at formerly active sites in spite of clear histological recovery. Among these pathways, the EMT pathway was specifically up-regulated only in active UC emphasizing the potential for cancer progression in these patients.
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China, Division of Allergy and Clinical Immunology, the Johns Hopkins School of Medicine, Baltimore, MD 21224, USA and.
authors.forename: Xinmei
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Division of Allergy and Clinical Immunology, the Johns Hopkins School of Medicine, Baltimore, MD 21224, USA and.
authors.forename: Jinshui
authors.initials: J
authors.lastname: Fan
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Fachao
authors.initials: F
authors.lastname: Zhi
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China, Department of Gastroenterology and Institute of Gastroenterology, Guangzhou First Municipal People's Hospital, Guangzhou Medical University, Guangzhou 510180, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Li
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: Division of Allergy and Clinical Immunology, the Johns Hopkins School of Medicine, Baltimore, MD 21224, USA and.
authors.forename: Alan E
authors.initials: AE
authors.lastname: Berger
authors.affiliation: Division of Allergy and Clinical Immunology, the Johns Hopkins School of Medicine, Baltimore, MD 21224, USA and.
authors.forename: Meher Preethi
authors.initials: MP
authors.lastname: Boorgula
authors.affiliation: Division of Allergy and Clinical Immunology, the Johns Hopkins School of Medicine, Baltimore, MD 21224, USA and.
authors.forename: Sangjucta
authors.initials: S
authors.lastname: Barkataki
authors.affiliation: Division of Allergy and Clinical Immunology, the Johns Hopkins School of Medicine, Baltimore, MD 21224, USA and.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Courneya
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Allergy and Clinical Immunology, the Johns Hopkins School of Medicine, Baltimore, MD 21224, USA and.
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Barnes
authors.affiliation: Division of Allergy and Clinical Immunology, the Johns Hopkins School of Medicine, Baltimore, MD 21224, USA and ccheadl@jhmi.edu.
authors.forename: Chris
authors.initials: C
authors.lastname: Cheadle
mesh_terms: D000328:Adult; D003093:Colitis, Ulcerative / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged
chemical_list: D016326:Extracellular Matrix Proteins; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1