Proteomics-Informed Identification of Luminal Targets For In Situ Diagnosis of Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) is a chronic condition resulting in impaired intestinal homeostasis. Current practices for diagnosis of IBD are challenged by invasive, demanding procedures. We hypothesized that proteomics analysis could provide a powerful tool for identifying clinical biomarkers for noninvasive IBD diagnosis. Here, the global intestinal proteomes from commonly used in vitro and in vivo models of IBD were analyzed to identify apical and luminal proteins that can be targeted by orally delivered diagnostic agents. Global proteomics analysis revealed upregulated plasma membrane proteins in intestinal segments of proximal-and distal colon from dextran sulfate sodium-treated mice and also in inflamed human intestinal Caco-2 cells pretreated with pro-inflammatory agents. The upregulated colon proteins in mice were compared to the proteome of the healthy ileum, to ensure targeting of diagnostic agents to the inflamed colon. Promising target proteins for future investigations of non-invasive diagnosis of IBD were found in both systems and included Tgm2/TGM2, Icam1/ICAM1, Ceacam1/CEACAM1, and Anxa1/ANXA1. Ultimately, these findings will guide the selection of appropriate antibodies for surface functionalization of imaging agents aimed to target inflammatory biomarkers in situ.

Severe COVID-19 Shares a Common Neutrophil Activation Signature with Other Acute Inflammatory States

“…Of note, these 11 genes encode proteins that are crucial for several pathways involved in neutrophil-mediated immunity, and are associated with diseases that increase the risk of severe COVID-19 [ 91 , 92 ], such as chronic obstructive pulmonary disease (COPD) [ 93 , 94 ] and ulcerative colitis [ 95 , 96 ] ( Supplementary Figure S6C and Supplementary Table S14 ). These 11 genes are also significantly different between COVID-19_ICU and COVID-19_nonICU ( Figure 6 D) in the bulk-RNA seq dataset (GSE157103, Overmyer et al 2020 [ 26 ]), indicating that these genes are consistently associated with COVID-19 severity across different patient cohorts.…”

Metabolomics Study of Shaoyao Plants Decoction on the Proximal and Distal Colon in Mice with Dextran Sulfate Sodium-Induced Colitis by UPLC-Q-TOF-MS

“… 60 , 61 The proximal colon was morphologically distinct from the remaining parts of the tissue by transverse folds that project into the lumen. 62 Then, the proximal colon and distal colon of each mouse were cut into pieces; one piece of the proximal colon and distal colon was fixed in 4% paraformaldehyde, and the remaining pieces from a colon were stored at −80 °C for subsequent use.…”

Severe COVID-19 shares a common neutrophil activation signature with other acute inflammatory states

“…Of note, these 11 genes encode proteins that are crucial for several pathways involved in neutrophil-mediated immunity, and are associated with diseases that increase the risk of severe COVID-19 73,74 such as chronic obstructive pulmonary disease (COPD) 75,76 and ulcerative colitis 77,78 (Supp. Figure 6E and Supp.…”

“…Among these 21 genes, 11 genes (among them also the 8 genes described above) were differentially expressed when comparing patients with mild and severe COVID-19 (Figure 7C). Of note, these 11 genes encode proteins that are crucial for several pathways involved in neutrophil-mediated immunity, and are associated with diseases that increase the risk of severe COVID-19 [91,92] such as chronic obstructive pulmonary disease (COPD) [93,94] and ulcerative colitis [95,96] (Supplementary Figure S6C and Supplementary Table S14). These 11 genes are also significantly different between COVID-19_ICU and COVID-19_nonICU (Figure 7D) in the bulk RNAseq dataset (GSE157103, Overmyer et al 2020 [26]), indicating that these genes are consistently associated with COVID-19 severity across different patient cohorts.…”