Heparin-binding EGF-like growth factor (HB-EGF) therapy for intestinal injury: Application and future prospects

Yang, Jianhong; Su, Yongfu; Zhou, Yu; Besner, Gail E.

doi:10.1016/j.pathophys.2013.11.008

Cited by 22 publications

(19 citation statements)

References 91 publications

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“…Heparin-binding EGF-like growth factor has been identified as a biologic agent capable of preventing NEC in various animal models and of reversing the effects of established NEC, via positive effects on mucosal healing 135 , intestinal stem cell function 136 and vascular perfusion 84,137 . A readily absorbed and nontoxic oligosaccharide that inhibits TLR4 was shown to prevent NEC in mice and piglets and to reduce intestinal inflammation in ex vivo human intestine obtained during the treatment of NEC 68 .…”

Section: Strategies For Nec Preventionmentioning

confidence: 99%

Necrotizing enterocolitis: new insights into pathogenesis and mechanisms

Niño

Sodhi

Hackam

2016

Nat Rev Gastroenterol Hepatol

430

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: Strategies For Nec Preventionmentioning

confidence: 99%

Necrotizing enterocolitis: new insights into pathogenesis and mechanisms

Niño

Sodhi

Hackam

2016

Nat Rev Gastroenterol Hepatol

430

394

View full text Add to dashboard Cite

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“…As a member of the EGF family, HB-EGF binds to the EGF receptor (EGFR) and has known mitogenic effects. HB-EGF is expressed in response to hypoxia, tissue damage, and oxidative stress, including in the intestine, and has a pivotal role in tissue regeneration and repair [31,32]. In seeking to evaluate the role of exogenous HB-EGF in the context of NEC, Dvorak and colleagues demonstrated that either the oral administration of HB-EGF or EGF significantly reduced NEC in a premature rat model through increased production of MUC2, a secretory mucin [33].…”

Section: Heparin-binding Epidermal Growth Factormentioning

confidence: 99%

A Review of the Immunomodulating Components of Maternal Breast Milk and Protection Against Necrotizing Enterocolitis

2019

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Breast milk contains immunomodulating components that are beneficial to newborns during maturation of their immune system. Human breast milk composition is influenced by an infant’s gestational and chronological age, lactation stage, and the mother and infant’s health status. Major immunologic components in human milk, such as secretory immunoglobulin A (IgA) and growth factors, have a known role in regulating gut barrier integrity and microbial colonization, which therefore protect against the development of a life-threatening gastrointestinal illness affecting newborn infants called necrotizing enterocolitis (NEC). Breast milk is a known protective factor in the prevention of NEC when compared with feeding with commercial formula. Breast milk supplements infants with human milk oligosaccharides, leukocytes, cytokines, nitric oxide, and growth factors that attenuate inflammatory responses and provide immunological defenses to reduce the incidence of NEC. This article aims to review the variety of immunomodulating components in breast milk that protect the infant from the development of NEC.

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“…Most of its distribution shortly after administration is within the plasma, liver, kidneys, bile, and urine. (Feng et al, 2006, Yang et al, 2014) The rapid decline of HB-EGF in plasma is dues to a rapid irreversible uptake process. (Burwen et al, 1985, Dunn and Hubbard, 1984, Kim et al, 1988, St Hilaire et al, 1983)Given its rapid distribution and elimination, it is not surprising that the small doses used in our study, even if delivered intravenously, cannot be detected above background levels.…”

Section: Discussionmentioning

confidence: 99%

No systemic exposure of transtympanic heparin-binding epidermal growth factor like growth factor

Maria

Kim

Yang

2016

Drug and Chemical Toxicology

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Context Heparin binding epidermal growth factor like growth factor (HB-EGF) is an emerging therapeutic for the regeneration of the tympanic membrane. Objective Our aim was to determine whether the doses of HB-EGF delivered in a sustained release hydrogel into a middle ear mouse model, would be measurable in the systemic circulation. We also aimed to observe, in the scenario that the intended dose was absorbed directly into the circulation, whether these levels could be measured above the background levels of HB-EGF in the circulation. Methods A total of 12 mice had trans tympanic injections of 5ug/ml of HB-EGF contained within a previously described novel hydrogel vehicle, while another 12 mice had intravenous delivery of 10ug/kg of HB-EGF. Intravenous blood samples were collected at 0, 3, 24, 168, 288 and 720 hours post injection. A double-antibody sandwich one-step process enzyme-linked immunosorbent assay (ELISA) was used to determine the level of HB-EGF in the serum. Results No mice in the trans tympanic administration group and no mice in the intravenous administration group were found to have blood level measured above that in the controls. Discussion The inability of the positive control to measure levels above background, suggest the total dose used in our studies, even if 100% absorbed into the system circulation is insignificant. Conclusions HB-EGF at the doses and delivery method proposed for treatment of chronic TM perforation in a mouse model are likely to have no measurable systemic effect.

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Heparin-binding EGF-like growth factor (HB-EGF) therapy for intestinal injury: Application and future prospects

Cited by 22 publications

References 91 publications

Necrotizing enterocolitis: new insights into pathogenesis and mechanisms

Necrotizing enterocolitis: new insights into pathogenesis and mechanisms

A Review of the Immunomodulating Components of Maternal Breast Milk and Protection Against Necrotizing Enterocolitis

No systemic exposure of transtympanic heparin-binding epidermal growth factor like growth factor

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