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Title: | Gene and Mirna Regulatory Networks During Different Stages of Crohn's Disease | Authors: | Verstockt, Sare De Hertogh, Gert Van der Goten, Jan Verstockt, Bram Vancamelbeke, Maaike Machiels, Kathleen Van Lommel, Leentje Schuit, Frans Van Assche, Gert Rutgeerts, Paul Ferrante, Marc Vermeire, Severine ARIJS, Ingrid Cleynen, Isabelle |
Issue Date: | 2019 | Publisher: | OXFORD UNIV PRESS | Source: | JOURNAL OF CROHNS & COLITIS, 13(7), p. 916-930 | Abstract: | Background and Aims: Early treatment of Crohn's disease [CD] is required in order to optimize patient outcomes. To this end, we need to gain a better understanding of the molecular changes at the onset of CD. Methods: As a model for the earliest mucosal CD lesions, we study post-operative recurrent CD [Rutgeerts score >= i2b]. We are the first to analyse gene and microRNA [miRNA] expression profiles in ileal biopsies from these patients, and compare them with those of newly diagnosed [<= 18 months] and late-stage [> 10 years after diagnosis] CD patients. Results: Except for one gene [WNT5A], there are no differential genes in CD patients without postoperative recurrence [i0], showing that previous disease did not influence gene expression in the neoterminal ileum, and that this model can be used to study early mucosal CD lesions. Gene expression and co-expression network dysregulation is more pronounced in newly diagnosed and late-stage CD than in post-operative recurrent CD, with most important modules associated with [a] granulocyte adhesion/diapedesis, and cholesterol biosynthesis. In contrast, we found a role for snoRNAs/miRNAs in recurrent CD, highlighting the potential importance of regulatory RNAs in early disease stages. Immunohistochemistry confirmed the expression of key dysregulated genes in damaged/regenerating epithelium and immune cells in recurrent CD. Conclusions: Aside from regulatory RNAs, there are no clear gene signatures separating postoperative recurrent, newly diagnosed, and late-stage CD. The relative contribution of dysregulated genes and networks differs, and suggests that surgery may reset the disease at the mucosal site, and therefore post-operative recurrent CD might be a good model a good model to study to study early mucosal CD lesions. | Notes: | [Verstockt, Sare; Cleynen, Isabelle] Katholieke Univ Leuven, Dept Human Genet, Lab Complex Genet, O&N4 Herestr 49,Box 610, B-3000 Leuven, Belgium. [De Hertogh, Gert] Univ Hosp, Dept Morphol & Mol Pathol, Leuven, Belgium. [De Hertogh, Gert] Katholieke Univ Leuven, Dept Imaging & Pathol, Translat Cell & Tissue Res, Leuven, Belgium. [Van der Goten, Jan; Verstockt, Bram; Vancamelbeke, Maaike; Machiels, Kathleen; Van Assche, Gert; Rutgeerts, Paul; Ferrante, Marc; Vermeire, Severine; Arijs, Ingrid] Katholieke Univ Leuven, Dept Chron Dis Metab & Aging CHROMETA, Translat Res Ctr Gastrointestinal Disorders TARGI, Leuven, Belgium. [Verstockt, Bram; Van Assche, Gert; Rutgeerts, Paul; Ferrante, Marc; Vermeire, Severine] Katholieke Univ Leuven, Univ Hosp, Dept Gastroenterol & Hepatol, Leuven, Belgium. [Van Lommel, Leentje; Schuit, Frans] Katholieke Univ Leuven, Dept Cellular & Mol Med, Gene Express Unit, Leuven, Belgium. [Arijs, Ingrid] Hasselt Univ, Fac Med & Life Sci, Hasselt, Belgium. [Arijs, Ingrid] Jessa Hosp, Hasselt, Belgium. | Keywords: | Early Crohn's disease; gene expression; gene regulation; molecular mechanisms;early Crohn’s disease; gene expression; gene regulation; molecular mechanisms | Document URI: | http://hdl.handle.net/1942/29853 | ISSN: | 1873-9946 | e-ISSN: | 1876-4479 | DOI: | 10.1093/ecco-jcc/jjz007 | ISI #: | 000485146200012 | Rights: | 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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