Altered Expression of the Epithelial Mucin MUC1 Accompanies Endoscopic Recurrence of Postoperative Crohn’s Disease

Abstract

Background: MUC1-glycoprotein is expressed at low levels and in fully glycosylated form on epithelial cells. Inflammation causes MUC1 overexpression and hypoglycosylation. We hypothesized that overexpression of hypoglycosylated MUC1 would be found in postoperative Crohn’s disease (CD) recurrence and could be considered an additional biomarker of recurrence severity. Methods: We examined archived neo-terminal ileum biopsies from patients with prior ileocecal resection who had postoperative endoscopic assessment of CD recurrence and given a Rutgeerts ileal recurrence score. Consecutive tissue sections were stained using 2 different anti-MUC1 antibodies, HMPV that recognizes all forms of MUC1 and 4H5 that recognizes only inflammation-associated hypoglycosylated MUC1. Results: A total of 71 postoperative CD patients were evaluated. There was significant increase in MUC1 expression of both glycosylated/normal (P<0.0001) and hypoglycosylated/abnormal (P<0.0001) forms in patients with severe endoscopic CD recurrence (i3+i4), ileal score i2, compared with patients in endoscopic remission (i0+i1). Results were similar regardless of anti-TNF-α use. Although MUC1 expression and Rutgeerts scores were in agreement when characterizing the majority of cases, there were a few exceptions where MUC1 expression was characteristic of more severe recurrence than implied by Rutgeerts score. Conclusions: MUC1 is overexpressed and hypoglycosylated in neo-terminal ileum tissue of patients with postoperative CD recurrence. Increased levels are associated with more severe endoscopic recurrence scores, and this is not influenced by anti-TNF-α use. Discrepancies found between Rutgeerts scores and MUC1 expression suggest that addition of MUC1 as a biomarker of severity of postoperative CD recurrence may improve categorization of recurrence status and consequently treatment decisions.

Ingested Engineered Nanomaterials Affect the Expression of Mucin Genes—An In Vitro-In Vivo Comparison

“…Moreover, we observed moderate decreases in the expression of MUC2 and MUC5AC under inflamed conditions. These findings agree with studies on IBD patients and mice with an artificially induced colitis [34,[96][97][98]. Contrasting our results, IBD has formerly been associated with higher expression levels of MUC5AC [34,98].…”

Identification of hub genes and key pathways in pediatric Crohn’s disease using next generation sequencing and bioinformatics analysis

“…A total of 957 DEGs were screened: 478 up regulated genes and 479 down regulated genes. Lee et al [41], Gijsbers et al [42], Hashash et al [43], Wnorowski et al [44] and Kyodo et al [45] found that FCGR3A, CXCL8, MUC1, HCAR3 and DUOX2 might play an important role in the pathophysiology of CD. Nourse et al [46] and Nakashima et al [47] found that FCGR3A and MUC1 was altered expressed in coagulation and fibrinolysis.…”

Intestinal mucosa-derived DNA methylation signatures in the penetrating intestinal mucosal lesions of Crohn’s disease

“…Mucin-1 was a major product which secreted by goblet cells 26 and was a component of ECM 27 . Recent studies 28 – 32 had found that the expression of MUC1 in CD was significantly increased. This was consistent with the fact that methylation of MUC1 was reduced in this study.…”