Gene and Mirna Regulatory Networks During Different Stages of Crohn’s Disease.
J Crohns Colitis. 2019 Jan 18;:
Authors: Verstockt S, De Hertogh G, Van der Goten J, Verstockt B, Vancamelbeke M, Machiels K, Van Lommel L, Schuit F, Van Assche G, Rutgeerts P, Ferrante M, Vermeire S, Arijs I, Cleynen I
Background/Aims: Early treatment of Crohn’s disease (CD) is required 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 this to newly diagnosed (≤18 months) and late (>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 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 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 to study early mucosal CD lesions.
PMID: 30657881 [PubMed – as supplied by publisher]