P107 Decreased epithelial keratinization contributes to defective wound healing in Crohn's disease fistula

Abstract Background Up to 30% of Crohn's Disease (CD) patients suffer from perianal fistula creating a high disease burden. Treating CD is challenging compared cryptoglandular fistula, which have significantly better wound healing response. Previous studies suggested epithelial mesenchymal transition as an inducer formation, markers were observed in tracts. However, most normal mucosa, thus disregarding whether any difference was fact sign (as will more active than uninjured mucosa) or pathology not occurring effectively). Therefore, this study we evaluated well both healthy mucosa (no healing) and (effective order determine the role differences found. Methods Biopsies internal opening (n=20) collected two publicly available datasets obtained un-inflamed rectum (RISK cohort GSE83245). In addition, curettage material (n=54) (n=15) obtained. Expression profiling performed using RNASeq. Results Comparing at rectum, 770 genes differentially expressed. Pathway analysis revealed upregulation proliferative inflammatory processes, consistent with expected immune responses. Interestingly, strongest seen for processes cornification keratinization, including expression IVL (involucrin) FLGR2 (fillagrin2), involved keratinocyte differentiation. To evaluate contributing rather persistent disease, analyzed actual tract fistula. Strikingly, keratinization pronounced suggesting effective CD. Similar data TGFb, previously detected considered pathological contributor. While confirm increased TGFb activity tracts higher Again, would suggest signaling part response pathogenic mechanism. Conclusion Perianal fistulas show pathways mucosa. saw involvement pathology.