scholarly journals The protective effect and mechanism of epidermal growth factor on necrotizing enterocolitis in a neonatal rat model

2021 ◽  
Vol 10 (4) ◽  
pp. 900-913
Author(s):  
Wenqian Chen ◽  
Changyi Yang ◽  
Heng Xue ◽  
Qi Huang
2002 ◽  
Vol 282 (1) ◽  
pp. G156-G164 ◽  
Author(s):  
Bohuslav Dvorak ◽  
Melissa D. Halpern ◽  
Hana Holubec ◽  
Catherine S. Williams ◽  
Debra L. McWilliam ◽  
...  

Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of prematurely born infants. Maternal milk plays an important protective role against NEC development and is the major source of epidermal growth factor (EGF) for neonates. The aim of this study was to examine the effect of orally administered EGF on the incidence of NEC in a neonatal rat model. Newborn rats were artificially fed either with growth factor-free rat milk substitute (RMS) or RMS supplemented with 500 ng/ml of EGF (RMS+EGF). Experimental NEC was induced by exposure to asphyxia and cold stress. Development of NEC was evaluated by gross and histological scoring of damage in the ileum. Ileal EGF receptor (EGF-R), EGF, and transforming growth factor-α mRNA expression was assessed by RT competitive-PCR, and the EGF-R was localized by immunohistochemistry. EGF supplementation of formula reduced the incidence and severity of NEC in rats (13/16 RMS vs. 4/13 RMS+EGF). Ileal EGF-R mRNA expression was markedly increased in the RMS group compared with RMS+EGF. Enhanced EGF-R expression in the RMS group was localized predominantly in the epithelial cells of injured ileum. These data suggest a new potential therapeutic approach for the prevention and treatment of NEC.


2005 ◽  
Vol 288 (4) ◽  
pp. G755-G762 ◽  
Author(s):  
Jessica A. Clark ◽  
Robert H. Lane ◽  
Nicole K. MacLennan ◽  
Hana Holubec ◽  
Katerina Dvorakova ◽  
...  

Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Although end-stage NEC is characterized histopathologically as extensive necrosis, apoptosis may account for the initial loss of epithelium before full development of disease. We have previously shown that epidermal growth factor (EGF) reduces the incidence of NEC in a rat model. Although EGF has been shown to protect intestinal enterocytes from apoptosis, the mechanism of EGF-mediated protection against NEC is not known. The aim of this study was to investigate if EGF treatment elicits changes in expression of apoptotic markers in the ileum during the development of NEC. With the use of a well-established neonatal rat model of NEC, rats were divided into the following three experimental groups: dam fed (DF), milk formula fed (NEC), or fed with formula supplemented with 500 ng/ml EGF (NEC+EGF). Changes in ileal morphology, gene and protein expression, and histological localization of apoptotic regulators were evaluated. Anti-apoptotic Bcl-2 mRNA levels were markedly reduced and pro-apoptotic Bax mRNA levels were markedly elevated in the NEC group compared with DF controls. Supplementation of EGF into formula significantly increased anti-apoptotic Bcl-2 mRNA, whereas pro-apoptotic Bax was significantly decreased. The Bax-to-Bcl-2 ratio for mRNA and protein was markedly decreased in NEC+EGF animals compared with the NEC group. The presence of caspase-3-positive epithelial cells was markedly reduced in EGF-treated rats. These data suggest that alteration of the balance between pro-and anti-apoptotic proteins in the site of injury is a possible mechanism by which EGF maintains intestinal integrity and protects intestinal epithelium against NEC injury.


2010 ◽  
Vol 138 (5) ◽  
pp. S-77
Author(s):  
Andrew Maynard ◽  
Katerina Dvorak ◽  
Ludmila Khailova ◽  
Kelly M. Arganbright ◽  
Ashish Kurundkar ◽  
...  

2012 ◽  
Vol 47 (9) ◽  
pp. 1652-1657 ◽  
Author(s):  
Ramazan Ozdemir ◽  
Sadık Yurttutan ◽  
Fatma Nur Sarı ◽  
Bulent Uysal ◽  
Hatice Germen Unverdi ◽  
...  

2021 ◽  
Vol 20 (9) ◽  
pp. 1855-1860
Author(s):  
Leibo Wang ◽  
Jianhua He ◽  
Ketao Xu ◽  
Weichao Zhu ◽  
Ketao Xu

Purpose: To investigate the differential expressions of transforming growth factor-β1 (TGF-β1), hypoxia inductive factor-1 (HIF-1), vascular endothelial growth factor (VEGF), α-smooth muscle protein (α-SMA) and E-cadherin in renal tissues of neonatal rat model of hydronephrosis.Methods: The neonatal rats (90) were randomly divided into sham group and model group. The rats in the model group were further divided into two subgroups: week 1 and week 12 after relief of obstruction, with 30 rats in each group. Six rats were taken from each group for the determination of renal histopathological changes. Levels of TGF-β1, HIF-1, VEGF, α-SMA and E-cadherin in renal tissues were compared for different pathological grades and at different time points of obstruction relief.Results: With increase in Elder grade, the concentrations of TGF-β1, HIF-1, VEGF and α-SMA in renal tissues of hydronephrosis neonatal rats were gradually increased, while the expression level of Ecadherin gradually decreased (p < 0.05). However, the concentrations of TGF-β1, HIF-1, VEGF and α-SMA in renal tissues were significantly reduced, while the expression level of E-adherin was upregulated with time after relief of obstruction (p < 0.05).Conclusion: These findings are of great significance in determining the degree of kidney injury and recovery, and for the development of drugs for the treatment of renal injury.


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