Heparin-Binding EGF-Like Growth Factor Promotes Intestinal Anastomotic Healing

Radulescu, Andrei; Zhang, Hong Yi; Chen, Chun-Liang; Chen, Yan; Zhou, Yu; Yu, Xiaoyi; Otabor, Iyore; Olson, Jacob K.; Besner, Gail E.

doi:10.1016/j.jss.2010.06.036

Cited by 28 publications

(36 citation statements)

References 46 publications

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“…These findings, in combination with our previous studies demonstrating that HB-EGF promotes intestinal restitution in vivo , 48, 49 support a potential future therapeutic role for HB-EGF in the promotion of cell migration and adhesion in processes such as wound healing and recovery from injury.…”

Section: Discussionsupporting

confidence: 80%

Heparin-binding EGF-like growth factor (HB-EGF) promotes cell migration and adhesion via focal adhesion kinase

Besner

2014

Journal of Surgical Research

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Background Cell migration and adhesion are essential in intestinal epithelial wound healing and recovery from injury. Focal adhesion kinase (FAK) plays an important role in cell-extra cellular matrix (ECM) signal transduction. We have previously shown that heparin-binding epidermal growth factor-like growth factor (HB-EGF) promotes intestinal epithelial cell (IEC) migration and adhesion in vitro. The current study was designed to determine whether FAK is involved in HB-EGF-induced IEC migration and adhesion. Materials and Methods A scrape wound healing model of rat intestinal epithelial cells (RIE-1 cells) was used to examine the effect of HB-EGF on FAK-dependent cell migration in vitro. Immunofluorescence and Western blot analyses were performed to evaluate the effect of HB-EGF on the expression of phosphorylated FAK (p-FAK). Cell adhesion assays were performed to determine the role of FAK in HB-EGF-induced cell adhesion on fibronectin (FN). Results HB-EGF significantly increased healing after scrape wounding, an effect that was reversed in the presence of a FAK inhibitor (FAK I-14) (both with p<0.05). HB-EGF increased p-FAK expression, and induced p-FAK redistribution and actin reorganization in migrating RIE-1 cells. Cell adhesion and spreading on FN were significantly increased by HB-EGF (p<0.05). FAK I-14 significantly inhibited both intrinsic and HB-EGF-induced cell adhesion and spreading on FN (both with p<0.05). Conclusions FAK phosphorylation and FAK-mediated signal transduction play essential roles in HB-EGF-mediated IEC migration and adhesion.

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Section: Discussionsupporting

confidence: 80%

Heparin-binding EGF-like growth factor (HB-EGF) promotes cell migration and adhesion via focal adhesion kinase

Besner

2014

Journal of Surgical Research

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“…However, isolated case reports continue to emerge that suggest heparin is able to promote tissue repair and inhibit inflammation in patients with burns (Ferreira Chacon et al, 2010). In animal models, application of heparin-binding epidermal growth factor-like growth factor (HB-EGF)-which is known to be upregulated both in human burn tissue and during healing of partial-thickness burn injuries specifically through potentiation of the expression of transforming growth factor-a, another member of the EGF family of growth factors involved in wound repair (Cribbs et al, 1998)-can promote healing of ileal tissue 120 after experimental reanastomosis surgery (Radulescu et al, 2011). Localization of HB-EGF through binding to HSPG facilitates juxtacrine inhibition of cell proliferation by this growth factor, and disruption of this binding allows the released HB-EGF to function as an autocrine mitogen (Prince et al, 2010).…”

Section: Would Healing and Tissue Repairmentioning

confidence: 99%

Pharmacology of Heparin and Related Drugs

et al. 2015

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“…We also showed that HB-EGF knockout (KO) mice subjected to I/R injury have significantly impaired angiogenesis compared to their wild type (WT) counterparts [31]. Additionally, we used a model of intestinal anastomotic wound healing to show that HB-EGF transgenic (TG) mice have significantly increased angiogenesis and improved anastomotic healing compared to their WT counterparts [73]. In separate studies, we have examined the effects of HB-EGF on pericytes.…”

Section: Effects Of Hb-egf During Intestinal Injurymentioning

confidence: 99%

“…However, upon exposure to intestinal injury, HB-EGF TG mice have increased resistance to HS/R [36] and experimental NEC [25]. In addition, overexpression of HB-EGF in HB-EGF TG mice promoted intestinal anastomotic wound healing [73]. Conversely, we have examined the effects of HB-EGF loss-of-expression on recovery from intestinal injury, and have found that HB-EGF KO mice have increased susceptibility to HS/R [49] and experimental NEC [24].…”

Section: Effects Of Hb-egf During Intestinal Injurymentioning

confidence: 99%

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

Yang

Zhou

et al. 2014

Pathophysiology

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Throughout the past 20 years, we have been investigating the potential therapeutic roles of heparin-binding EGF-like growth factor (HB-EGF), a member of the epidermal growth factor family, in various models of intestinal injury including necrotizing enterocolitis (NEC), intestinal ischemia/reperfusion (I/R) injury, and hemorrhagic shock and resuscitation (HS/R). Our studies have demonstrated that HB-EGF acts as an effective mitogen, a restitution-inducing reagent, a cellular trophic factor, an anti-apoptotic protein and a vasodilator, via its effects on various cell types in the intestine. In the current paper, we have reviewed the application and therapeutic effects of HB-EGF in three classic animal models of intestinal injury, with particular emphasis on its protection of the intestines from NEC. Additionally, we have summarized the protective functions of HB-EGF on various target cells in the intestine. Lastly, we have provided a brief discussion focusing on the future development of HB-EGF clinical applications for the treatment of various forms of intestinal injury including NEC.

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Heparin-Binding EGF-Like Growth Factor Promotes Intestinal Anastomotic Healing

Cited by 28 publications

References 46 publications

Heparin-binding EGF-like growth factor (HB-EGF) promotes cell migration and adhesion via focal adhesion kinase

Heparin-binding EGF-like growth factor (HB-EGF) promotes cell migration and adhesion via focal adhesion kinase

Pharmacology of Heparin and Related Drugs

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

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