Gene and Mirna Regulatory Networks During Different Stages of Crohn’s Disease

Autor: Bram Verstockt, Severine Vermeire, Kathleen Machiels, Paul Rutgeerts, Ingrid Arijs, Jan Van der Goten, Leentje Van Lommel, Frans Schuit, Maaike Vancamelbeke, Marc Ferrante, Gert De Hertogh, Isabelle Cleynen, Gert Van Assche, Sare Verstockt
Přispěvatelé: 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
Rok vydání: 2019
Předmět:
Zdroj: Journal of Crohn's and Colitis. 13:916-930
ISSN: 1876-4479
1873-9946
DOI: 10.1093/ecco-jcc/jjz007
Popis: 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 post-operative 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 post-operative 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.
Databáze: OpenAIRE
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