Quantitative Proteomic Analysis Reveals the Deregulation of Nicotinamide Adenine Dinucleotide Metabolism and CD38 in Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) has become a major health challenge worldwide. However, the precise etiological and pathophysiological factors involved in IBD remain unclear. Proteomics can be used for large-scale protein identification analysis. In the current study, using tandem mass tag- (TMT-) based shotgun proteomics, proteomic differences between intestinal tissue from health controls, patients with Crohn’s disease (CD), and patients with ulcerative colitis (UC) were compared. Proteins with fold change >2 or <0.5 and P value < 0.05 between groups were considered differentially expressed. ProteinAtlas was used to analyze the tissue specificity of differentially expressed proteins (DEPs). Reactome pathway analysis was applied to cluster functional pathways. A total of 4786 proteins were identified, with 59 proteins showing higher levels and 43 showing lower levels in patients with IBD than in controls. Seventeen proteins, including angiotensin converting enzyme 2 (ACE2) and angiotensin converting enzyme 1 (ACE), showed higher levels in CD than in UC. Several novel proteins such as CD38, chitinase 3-like 1 (CHI3L1), olfactomedin 4 (OLFM4), and intelectin 1 were screened out between patients with IBD and controls. When proteins with fold change >1.2 or <0.84 and P value < 0.05 between groups were considered differentially expressed, the expression of 10 proteins, including CD38, involved in the nicotinamide adenine dinucleotide (NAD) metabolism and signaling pathway showed significant changes in IBD. Using the NCBI GEO database, we confirmed increased CD38 mRNA expression in patients with UC and in mouse colitis models. Protein CD38 expression was higher in CD and UC than in normal controls. CD38 expression was higher in inflamed tissues than in noninflamed tissues, and CD38 was located in F4/80-positive cells. Our study may provide novel insights into the molecular pathogenesis of IBD. Further studies are required on the role of NAD metabolism and CD38 in intestinal inflammation.

2019 novel coronavirus disease (COVID‐19) in patients with inflammatory bowel diseases

“…24,25 ACE2 is overexpressed in the inflamed GI tract of IBD patients, 26 with significantly higher expression in CD than in UC. 27 These findings could explain the high rate of GI symptoms in IBD patients with COVID-19…”

COVID-19 and immunomodulation in IBD

“…A study using tandem mass tag-based shotgun proteomics additionally showed higher levels of ACE2 in inflamed intestinal areas in patients (CD) as compared with patients with UC. 41 Finally, the fusion of SARS-CoV2 with the host cell membrane is critical for uptake in cells and is modulated by the S protein. Activation of the S protein via proeolytic cleavage is controlled by host trypsin-like proteases, whose activity is upregulated in IBD, and this effect might facilitate infection in patients with IBD.…”

Review article: prevention, diagnosis and management of COVID‐19 in the IBD patient

“…As gastrointestinal tract permeability may be increased in IBD patients 18 with higher expression of ACE2 in inflamed bowel, 48 there is also a theoretical increased risk of SARS‐CoV‐2 infection via the gut in IBD patients. Despite this, there is no current evidence of increased infection rates or worse disease severity of COVID‐19 in IBD patients.…”