Paneth cell proteins DEFA6 and GUCA2A as tissue markers in necrotizing enterocolitis

Abstract

Previous studies suggest that Paneth cells are involved in NEC development. Defensin alpha 6 (DEFA6) and guanylate cyclase activator 2A (GUCA2A) are selective protein markers of Paneth cells. The objective was to explore DEFA6 and GUCA2A expression in intestinal tissue samples from newborn infants with and without NEC. Tissue samples from histologically intact intestine were analyzed from 70 infants: 43 underwent bowel resection due to NEC and 27 controls were operated due to conditions such as intestinal atresia, dysmotility, aganglionosis, pseudo-obstruction or volvulus. Each tissue sample was immunohistochemically stained for DEFA6 and GUCA2A. Semi-automated digital image analysis was performed to determine protein expression. Clinical data and protein expressions were compared between the groups. DEFA6 expression was lower in the NEC group (p = 0.006). Low DEFA6 correlated with risk of developing NEC in a logistic regression analysis, independently of gestational age and birth weight (OR 0.843 [CI 0.732–0.971]; p = 0.018). GUCA2A expression did not differ between the two groups.Conclusion: Lower expression of DEFA6 together with intact GUCA2A expression indicates that NEC patients have well-defined Paneth cells but diminished defensin activity. Our results suggest that DEFA6 could be used as a biomarker for NEC. What is Known:• Previous studies of defensin activity in NEC have been inconsistent, showing that defensin levels may be increased or diminished in NEC. GUCA2A has to our knowledge never been studied in NEC. What is New:• This study benchmarks two specific Paneth cell markers (DEFA6 and GUCA2A) and their activity in individuals with and without NEC.• The key finding is that the NEC group had a lower DEFA6 expression compared to the Controls, while the expression of GUCA2A did not differ between the groups.

Single-Cell Profiling Reveals the Impact of Genetic Alterations on the Differentiation of Inflammation-Induced Murine Colon Tumors

“…Paneth cells are known to be the source of the antimicrobial hormones, GUCA2A and REG3G, which play an essential role in intestinal homeostasis [ 75 , 76 ]. We previously demonstrated through bulk RNA-seq that ETBF induces an increase in Reg3g expression in BLM tumors compared to Min tumors [ 27 ].…”

Single-cell profiling reveals the impact of genetic alterations on the differentiation of inflammation-induced colon tumors

“…Further investigation is required to study how BRAF V600E regulates Cdx2 expression in ETBF-induced colon tumors. Paneth cells are known to be the source of the antimicrobial hormones, GUCA2A and REG3G, which play an essential role in intestinal homeostasis (Hoffsten et al, 2023;Shin et al, 2023). We previously demonstrated through bulk RNA-seq that ETBF induces an increase in Reg3g expression in BLM tumors compared to Min tumors (Destefano Shields et al, 2021).…”

Reduced Expression of REG4 as a Sign of Altered Goblet Cell Function in Necrotizing Enterocolitis

“…10 The protective mucus layer acts as a physical barrier against pathogens. 10 The mucus also plays an important role in the immune system, together with the antimicrobial peptides excreted from Paneth cells 11 and other intestinal epithelial cells. 12,13 A dysfunctional intestinal barrier has been proposed to play a key role in NEC development, 14,15 and specifically, impaired mucin secretion.…”