The role of growth factors in intestinal regeneration and repair in necrotizing enterocolitis

Rowland, Kathryn J.; Choi, Pamela M.; Warner, Brad W.

doi:10.1053/j.sempedsurg.2013.01.007

Cited by 41 publications

(35 citation statements)

References 273 publications

(254 reference statements)

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“…Counter-regulatory factors can be exploited in order to dampen TLR4 signalling and expression to prevent the development of NEC. Natural factors include: epidermal growth factor (EGF) 71,140,185,186 , heparin-binding EGF-like growth factor (HB-EGF) 186–188 , nod-like receptor 2 (NOD2) 189 , Toll-like receptor 9 (TLR9) 67,190 , Platelet-activating factor acetylhydrolase (PAF-AH) 90 . Exogenous factors include: the small-molecule TLR4 inhibitor C34 (REF.…”

Section: Figurementioning

confidence: 99%

Necrotizing enterocolitis: new insights into pathogenesis and mechanisms

Niño

Sodhi

Hackam

2016

Nat Rev Gastroenterol Hepatol

429

394

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Necrotizing enterocolitis (NEC) is the most frequent and lethal disease of the gastrointestinal tract of preterm infants. At present, NEC is thought to develop in the premature host in the setting of bacterial colonization, often after administration of non-breast milk feeds, and disease onset is thought to be due in part to a baseline increased reactivity of the premature intestinal mucosa to microbial ligands as compared with the full-term intestinal mucosa. The increased reactivity leads to mucosal destruction and impaired mesenteric perfusion and partly reflects an increased expression of the bacterial receptor Toll-like receptor 4 (TLR4) in the premature gut, as well as other factors that predispose the intestine to a hyper-reactive state in response to colonizing microorganisms. The increased expression of TLR4 in the premature gut reflects a surprising role for this molecule in the regulation of normal intestinal development through its effects on the Notch signalling pathway. This Review will examine the current approach to the diagnosis and treatment of NEC, provide an overview of our current knowledge regarding its molecular underpinnings and highlight advances made within the past decade towards the development of specific preventive and treatment strategies for this devastating disease.

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Section: Figurementioning

confidence: 99%

Necrotizing enterocolitis: new insights into pathogenesis and mechanisms

Niño

Sodhi

Hackam

2016

Nat Rev Gastroenterol Hepatol

429

394

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“…EGF [21], IGF1 [3], and IGF2 [22] are known intestinotrophic factors. Systemic administration of these growth factors has shown to magnify adaptive intestinal mucosal growth after SBR [3, 8].…”

Section: Discussionmentioning

confidence: 99%

Both epidermal growth factor and insulin-like growth factor receptors are dispensable for structural intestinal adaptation

Sun

Diaz-Miron

Choi

et al. 2015

Journal of Pediatric Surgery

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Purpose Intestinal adaptation structurally represents increases in crypt depth and villus height in response to small bowel resection (SBR). Previously, we found that neither epidermal growth factor receptor (EGFR) nor insulin-like growth factor 1 receptor (IGF1R) function was individually required for normal adaptation. In this study, we sought to determine the effect of disrupting both EGFR and IGF1R expression on resection-induced adaptation. Methods Intestinal-specific EGFR and IGF1R double knockout mice (EGFR/IGF1R-IKO) (n=6) and wild-type (WT) control mice (n=7) underwent 50% proximal SBR. On postoperative day (POD) 7, structural adaptation was scored by measuring crypt depth and villus height. Rates of crypt cell proliferation, apoptosis, and submucosal capillary density were also compared. Results After 50% SBR, normal adaptation occurred in both WT and EGFR/IGF1R-IKO. Rates of proliferation and apoptosis were no different between the two groups. The angiogenic response was less in the EGFR/IGF1R-IKO compared to WT mice. Conclusion Disrupted expression of EGFR and IGF1R in the intestinal epithelial cells does not affect resection-induced structural adaptation but attenuates angiogenesis after SBR. These findings suggest that villus growth is driven by receptors and pathways that occur outside the epithelial cell component, while angiogenic responses may be influenced by epithelial-endothelial crosstalk.

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“…The protective function of the intestinal mucosal barrier depends on the expression and properties of mucins 8 and antimicrobial defensive factors, which are involved in the regulatory system and generate the main chain of host defence against pathogens 9 . Mucins are actively expressed in the epithelium of the gastrointestinal tract and form the high-molecularweight viscoelastic layer, which is the protective barrier between the mucosal surface of the abdominal contents of the gastrointestinal tract, representing a nourishing environment for vital activity of commensal bacteria of the intestine 10,11 .…”

Section: Ijpsr (2017) Volume 8 Issue 7 (Research Article)mentioning

confidence: 99%

Untitled

2017

IJPSR

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Perinatal hypoxia results in poor circulation in internal organs, causing damage to the intestinal mucosa. Here, we aimed to evaluate the role of endothelial vasoconstrictor function in the formation of the intestinal mucous barrier in low-birth-weight neonates with hypoxicischemic encephalopathy (HIE). We comparatively analysed the concentrations of specific intestinal protective markers, i.e., serum mucin 2 (MUC2), serum intestinal trefoil factor (ITF), and faecal human β-defensin 2 (HBD2), and a marker of endothelial activity, i.e., serum endothelin-1 (ET-1), in early of postnatal life in 8 infants with moderate/severe HIE (group 1), 14 neonates with mild HIE (group 2), and 20 control infants using standard enzyme-linked immunosorbent assays. Markers of intestinal mucosa activity were not differentially expressed between infants in groups 1 and 2. Mean total concentrations of ITF and HBD2 were higher in groups 1 and 2 than in the control group (p < 0.05). In contrast, MUC2 concentrations were lower in infants of groups 1 and 2 than in the control infants. ET-1 expression was higher in group 2 than in group 1 and the control group on days 1-3 (p < 0.05). Spearman's rank-order correlation analysis showed that there were no significant relationships of ET-1 with MUC2 and HBD2. However, there was a significant negative correlation between ET-1 and ITF in group 1 infants. High serum ITF and faeces HBD2 levels accompanied low blood concentrations of MUC2, reflecting the depletion of Goblet cell function in response to hypoperfusion in low-birth-weight infants with HIE.

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The role of growth factors in intestinal regeneration and repair in necrotizing enterocolitis

Cited by 41 publications

References 273 publications

Necrotizing enterocolitis: new insights into pathogenesis and mechanisms

Necrotizing enterocolitis: new insights into pathogenesis and mechanisms

Both epidermal growth factor and insulin-like growth factor receptors are dispensable for structural intestinal adaptation

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