P020 Differential expression of miR-424-5p and miR-378c in stenotic and penetrating lessions of Crohn’s Disease associates with altered transcription of genes involved in vascular regulation

Coll, S.(1);Seco, M.(1);Bauset, C.(1);Lis, L.(1);Cosín-Roger, J.(2);Ortiz-Masia, D.(3);Gisbert-Ferrandiz, L.(1);Barrachina, D.(1);Calatayud, S.(1);

(1)Faculty of Medicine - University of Valencia, Pharmacology, Valencia, Spain;(2)FISABIO, Unidad Mixta Facultad de Medicina-Hospital Dr Peset, Valencia, Spain;(3)Faculty of Medicine - University of Valencia, Medicine, Valencia, Spain;

Background

Crohn´s disease (CD) is often complicated by the appearance of intestinal stenosis (B2 behaviour) or fistulas (B3 behaviour), and the factors determining the pattern of disease and the etiology of these lesions, both associated with fibrosis and requiring surgery, are poorly defined. Our aim has been to detect transcriptomic alterations in intestinal tissues affected by stenosis or fistulas, and have centred our attention in genes affecting vessel formation and function as potential contributors to these lesions.

Methods

We conducted a small RNA sequencing profiling on ileal surgical resections from CD patients with B2 (n=10) or B3 (n=10) behaviour. We obtained a sample from affected tissue and the paired non-affected ileum from each patient.

Results

Tissues affected by stenotic or penetrating lesions present a differential expression of two pro-angiogenic miRNAs (Fig1A) and an increased expression of genes associated with vascular regulation (Fig1B), and both alterations are more pronounced in penetrating lesions. The expression of this set of genes shows a generalized and significant correlation with that of the pro-angiogenic miRNAs (negative with the down-regulated miR-378c, positive with the up-regulated miR-424-5p, Fig1C), especially in the affected tissue.


Fig1. Expression of pro-angiogenic miRNAs (A) and of genes associated with vascular regulation (B) in tissues from stenotic (B2) and penetrating (B3) lesions of CD patients. Data represent normalized counts of each RNA and are expressed as mean±SEM (A) or mean (B). Data in (C) correspond to Pearson’s R. Significant differences vs corresponding non-affected tissue are represented by *P<0.05 (paired t-test) and #P<0.05 (ANOVA+Tukey test)

Conclusion

Ileal tissues from CD patients affected by stenosis or penetrating injuries present a local alteration in the expression of miRNAs with pro-angiogenic functions that probably contributes to the up-regulation of genes associated with vessel formation and to the modification of the vascular compartment in these lesions.