Paneth cell proteins DEFA6 and GUCA2A as tissue markers in necrotizing enterocolitis (original) (raw)
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Diminished DEFA6 Expression in Paneth Cells Is Associated with Necrotizing Enterocolitis
Gastroenterology Research and Practice, 2018
Background. Necrotizing enterocolitis (NEC) is the most common gastrointestinal disorder in premature infants with a high morbidity and mortality. Paneth cell dysfunction has been suggested to be involved in the pathogenesis of NEC. Defensin alpha-6 (DEFA6) is a specific marker for Paneth cells acting as part of the innate immunity in the human intestines. The aim of this study was to investigate the expression of DEFA6 in infants with NEC.Materials and Methods. Infants who underwent bowel resection for NEC at level III NICU in Sweden between August 2004 and September 2013 were eligible for the study. Macroscopically vital tissues were selected for histopathological evaluation. All infants in the control group underwent laparotomy and had ileostomy due to dysmotility, and samples were taken from the site of the stoma. DEFA6 expression was studied by immunohistochemistry. Digital image analysis was used for an objective and precise description of the samples.Results. A total of 12 in...
PloS one, 2018
Necrotizing enterocolitis (NEC) remains the leading cause of gastrointestinal morbidity and mortality in premature infants. Human and animal studies suggest a role for Paneth cells in NEC pathogenesis. Paneth cells play critical roles in host-microbial interactions and epithelial homeostasis. The ramifications of eliminating Paneth cell function on the immature host-microbial axis remains incomplete. Paneth cell function was depleted in the immature murine intestine using chemical and genetic models, which resulted in intestinal injury consistent with NEC. Paneth cell depletion was confirmed using histology, electron microscopy, flow cytometry, and real time RT-PCR. Cecal samples were analyzed at various time points to determine the effects of Paneth cell depletion with and without Klebsiella gavage on the microbiome. Deficient Paneth cell function induced significant compositional changes in the cecal microbiome with a significant increase in Enterobacteriacae species. Further, the...
Biomarkers for Infants at Risk for Necrotizing Enterocolitis: Clues to Prevention?
Pediatric Research, 2009
Necrotizing enterocolitis (NEC) is the most common severe gastrointestinal emergency that affects premature newborns. This disease often has a rapid onset with few, if any, antecedent signs that can be used to reliably predict its occurrence. Its rapid onset and progression to death, as well as its severe morbidity when the infant survives, begs for early diagnostic tools that may be used in determining those infants who would be at greatest risk for development of the disease and for whom early preventative measures could be targeted. Although studies have suggested efficacy of several techniques such as breath hydrogen, inflammatory mediators in blood, urine or stool, and genetic markers, these all have drawbacks limiting their use. The application of newly developed "omic" approaches may provide biomarkers for early diagnosis and targeted prevention of this disease.
Necrotizing enterocolitis is associated with neonatal intestinal injury
Journal of Pediatric Surgery, 2011
PURPOSE: We hypothesized that a subset of premature newborns has subclinical, intestinal mucosal compromise that predisposes to the development of necrotizing enterocolitis (NEC) days or weeks later. METHODS: Fifty-five newborns of 23 to 36 weeks' gestational age were identified, and urine was collected over the first 90 hours of life. The urinary concentration of intestinal fatty acid binding protein (iFABP(u)), a sensitive marker for intestinal injury, was determined. The diagnosis of NEC was based upon clinical condition, pathology, and/or imaging findings. RESULTS: Neonatal iFABP(u) exceeded 800 pg/mL in 27 subjects, including 9 of 9 who subsequently developed stage 2 or 3 NEC. This degree of iFABP(u) elevation, but not asphyxia, was significantly associated with the development of NEC (P < .01). CONCLUSION: In this population of premature newborns, there was a substantial incidence of intestinal mucosal compromise. All infants who subsequently developed stage 2 or 3 NEC had an elevated iFABP(u). This finding suggests a model for the pathogenesis of some cases of NEC, whereby perinatal mucosal injury predisposes to further damage when feedings are initiated. In addition, neonatal iFABP(u) assessment may represent a tool to identify infants at the highest risk for NEC and allow for the institution of focused, preventive measures.
Paneth Cells and Antibacterial Host Defense in Neonatal Small Intestine
Infection and Immunity, 2005
Paneth cells are specialized epithelia in the small bowel that secrete antimicrobial proteins. Paneth cells are vital to the innate immunity of the small bowel in adult mammals, but their role during neonatal infection of the small bowel is not well established. Dithizone selectively damages Paneth cells, and when dithizone-treated newborn rats are infected enterally with Escherichia coli, the numbers of E. coli cells in their jejunal and ileal lavage fluid are significantly increased compared to controls. The data support that Paneth cells are necessary for neonatal antibacterial defense.
Intestinal proteome changes during infant necrotizing enterocolitis
Pediatric Research, 2012
Background: changes in the intestinal and colonic proteome in patients with necrotizing enterocolitis (Nec) may help to characterize the disease pathology and identify new biomarkers and treatment targets for Nec. Methods: Using gel-based proteomics, proteins in Necaffected intestinal and colonic sections were compared with those in adjacent, near-normal tissue sections within the same patients. Western blot and immunohistochemistry were applied to crossvalidate proteomic data and histological location of some selected proteins. results: Thirty proteins were identified with differential expression between necrotic and vital small-intestine sections and 23 proteins were identified for colon sections. Five proteins were similarly affected in the small intestine and colon: histamine receptors (hRs), actins, globins, immunoglobulin, and antitrypsin. Two heat shock proteins (hsPs) were affected in the small intestine. Furthermore, proteins involved in antioxidation, angiogenesis, cytoskeleton formation, and metabolism were affected. Finally, secretory proteins such as antitrypsin, fatty-acid binding protein 5, and haptoglobin differed between Nec-affected and vital tissues. conclusion: Nec progression affects different pathways in the small intestine and colon. hsPs may play an important role, especially in the small intestine. The identified secretory proteins should be investigated as possible circulating markers of Nec progression in different gut regions.
Single cell atlas of the neonatal small intestine with necrotizing enterocolitis
2022
Necrotizing enterocolitis (NEC) is a gastrointestinal complication of premature infants with high rates of morbidity and mortality. A comprehensive view of the cellular changes and aberrant interactions that underlie this disease is lacking. Here, we combine single cell RNA sequencing, T Cell Receptor beta (TCRβ) analysis, bulk transcriptomics, and imaging to characterize cell identities, interactions and zonal changes in NEC. We find that inflammatory macrophages are abundant in NEC and that T cells exhibit increased expression of inflammatory genes and cytokines accompanied by an increase in TCRβ clonal expansion. Fibroblasts and endothelial cells increase in proportion and exhibit a switch to an activated pro-inflammatory state. Villus tip epithelial cell identity is substantially reduced in NEC and the remaining epithelial cells up-regulate pro-inflammatory genes. We establish a detailed map of aberrant epithelial-mesenchymal-immune interactions that may be driving inflammation ...
The Pathophysiology of Necrotizing Enterocolitis
NeoReviews, 2001
Objectives After completing this article, readers should be able to: 1. Describe the basic epidemiologic aspects of neonatal enterocolitis (NEC). 2. List the major risk factors that predispose neonates to NEC. 3. Delineate the current views on the mechanisms involved in the pathogenesis of NEC. 4. Discuss the various models used to study NEC. 5. List the major mediators believed to be involved in the pathogenesis of NEC.
Current concepts regarding the pathogenesis of necrotizing enterocolitis
Pediatric Surgery International, 2009
Necrotizing enterocolitis (NEC) is a devastating disease that predominantly affects premature neonates. The mortality associated with NEC has not changed appreciably over the past several decades. The underlying etiology of NEC remains elusive, although bacterial colonization of the gut, formula feeding, and perinatal stress have been implicated as putative risk factors. The disease is characterized by massive epithelial destruction, which results in gut barrier failure. The exact molecular and cellular mechanisms involved in this complex disease are poorly understood. Recent studies have provided significant insight into our understanding of the pathogenesis of NEC. Endogenous mediators such as prostanoids, cyclooxygenases, and nitric oxide may play a role in the development of gut barrier failure. Understanding the structural architecture of the gut barrier and the cellular mechanisms that are responsible for gut epithelial damage could lead to the development of novel diagnostic, prophylactic and therapeutic strategies in NEC.