Further evidence that epidermal growth factor enhances the intestinal adaptation following small bowel transplantation

Nakai, Kenta; Hamada, Y.; Kato, Yasunori; Kitagawa, K.; Hioki, Koshiro; Ito, Seiji; Okumura, Tadayoshi

doi:10.1016/j.lfs.2004.04.018

Cited by 6 publications

(4 citation statements)

References 40 publications

(40 reference statements)

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“…Epidermal growth factor (EGF), a small mitogenic polypeptide comprising 53 amino acid residues is typically present at about 1500 ng/ml and 124 ng/ml in porcine colostrum and mature milk, respectively [ 12 ]. EGF is synthesized in the salivary glands and kidneys and, to a lesser extent, in the lactating mammary glands, small intestine, liver and pancreas [ 13 ]-[ 15 ]. EGF has high stability in the gastrointestinal tract of human, mouse, rat and pig, especially in the gastric lumen and the proximal and mid-intestine lumen, with a higher degradation in the distal intestine lumen [ 16 ]-[ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Recombinant porcine epidermal growth factor-secreting Lactococcus lactispromotes the growth performance of early-weaned piglets

DingYue

Lin

et al. 2014

BMC Vet Res

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BackgroundEpidermal growth factor (EGF) is an important growth factor in regulation of cell proliferation, differentiation, survival and apoptosis. Studies showed that food-grade Lactococcus lactis (L. lactis) and NICE expression system have superior performance in exogenous protein expression. This study aimed to construct and express porcine EGF (pEGF), and use L. lactis as vehicle for producing and delivering pEGF. Furthermore, investigating biological activity of pEGF and exploring applications feasibility of combination effects of L. lactis and pEGF on early weaned piglets’ production.ResultsA recombinant Lactococcus lactis which produced and secreted pEGF at 1000 ng/ml in culture supernatant was generated. Secreted pEGF was a fully biologically active protein, as demonstrated by its capacity to stimulate L929 mouse fibroblast cell line proliferation in vitro. For in vivo study, forty piglets were randomly allocated to control, antibiotic control, empty vector-expressing L. lactis (LL-EV) and pEGF-secreting L. lactis (LL-pEGF). After 14 d of rearing, final body weight and average daily gain in LL-pEGF were greater (P < 0.05, 8.95 vs. 8.37 kg, 206.1 vs. 157.7 g/day, respectively) than those in control, but no significant differences between LL-pEGF, LL-EV and antibiotic control. Overall period average daily feed intake was higher in LL-pEGF, LL-EV and antibiotic control than in control (P < 0.05, 252.9, 255.6, 250.0, 207.3 g/day, respectively). No significant difference was observed on ADFI/ADG. LL-pEGF increased villous height in the duodenum, jejunum and ileum than in control and LL-EV (P < 0.05). Sucrase in the 3 intestinal segments, aminopeptidase A in the duodenum and Jejunum, aminopeptidase N and dipeptidase IV in the duodenum in LL-pEGF were higher than those in control (P < 0.05). Furthermore, Escherichia coli and Enterococcus counts decreased in the ileum and Lactobacillus increased in the ileum and cecum digesta in LL-pEGF compare with the control (P < 0.05). Lactobacillus increased in the cecum in LL-EV compared with control and antibiotic control (P < 0.05).ConclusionWe have generated a recombinant Lactococcus lactis which produced and secreted fully biologically active porcine EGF. Oral administration of pEGF-secreting L. lactis had beneficial effects on intestinal health and performance of early-weaned piglets.

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Section: Introductionmentioning

confidence: 99%

Recombinant porcine epidermal growth factor-secreting Lactococcus lactispromotes the growth performance of early-weaned piglets

DingYue

Lin

et al. 2014

BMC Vet Res

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“…EGF inhibits acid secretion, protects gastric mucosa against injury, exerts a trophic effect on gastroduodenal mucosa, mediates mucosal adaptation, and accelerates gastroduodenal ulcer healing by stimulating cell migration and proliferation (Tamawski and Jones 1998). Recent reports indicate that EGF enhances the structural and functional adaptation of intestinal grafts and may be a useful therapy after small bowel transplantation (SBT) (Nakai et al, 2004). Recent reports indicate that EGF enhances the structural and functional adaptation of intestinal grafts and may be a useful therapy after small bowel transplantation (SBT) (Nakai et al, 2004).…”

Section: Hormones and Trophic Factorsmentioning

confidence: 99%

Short Bowel Syndrome in Childhood

Höllwarth¹

2014

Colloquium Series on Integrated Systems Physiology: From Molecule to Function

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“…We have reported that EGF stimulates the intestinal structure and function in a rat model of isograft (16) and allograft (17,24). Recently, Azuara et al (1) demonstrated that administration of NO with caspase inhibitor minimizes BT in SBT, suggesting that NO prevents increased BT, although it induces an apoptotic effect.…”

mentioning

confidence: 91%

Epidermal growth factor and interleukin-1β synergistically stimulate the production of nitric oxide in rat intestinal epithelial cells

Kitagawa¹,

Hamada²,

Kato³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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growth factor (EGF) is one of the trophic factors for intestinal adaptation after small bowel transplantation (SBT). A recent report indicates that nitric oxide (NO) has cytoprotective effects on bacterial translocation (BT) after SBT. We hypothesized that EGF stimulates the expression of the inducible NO synthase (iNOS) gene in the graft after SBT, followed by increased production of NO, resulting in the decrease of BT. Intestinal epithelial cells (IEC)-6 were treated with EGF and/or IL-1␤ in the presence and absence of phosphatidylinositol 3-kinase (PI3-kinase) and EGF receptor kinase inhibitors (LY-294002 and tyrphostin A25). The induction of NO production and iNOS and its signal molecules, including the inhibitory protein of NF-B (IB), NF-B, and Akt, were analyzed. IL-1␤ stimulated the degradation of IB and the activation of NF-B but had no effect on iNOS induction. EGF, which had no effect on the NF-B activation and iNOS induction, stimulated the upregulation of type 1 IL-1 receptor (IL-1R1) through PI3-kinase/Akt. Simultaneous addition of EGF and IL-1␤ stimulated synergistically the induction of iNOS, leading to the increased production of NO. Our results indicate that EGF and IL-1␤ stimulate two essential signals for iNOS induction in IEC-6 cells: the upregulation of IL-1R1 through PI3-kinase/Akt and the activation of NF-B through IB kinase, respectively. Simultaneous addition of EGF and IL-1␤ can enhance the production of NO, which may contribute to the cytoprotective effect of EGF against intestinal injury. inducible nitric oxide synthase; nuclear factor-B; phosphatidylinositol 3-kinase; Akt; type 1 interleukin-1 receptor.

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Further evidence that epidermal growth factor enhances the intestinal adaptation following small bowel transplantation

Cited by 6 publications

References 40 publications

Recombinant porcine epidermal growth factor-secreting Lactococcus lactispromotes the growth performance of early-weaned piglets

Recombinant porcine epidermal growth factor-secreting Lactococcus lactispromotes the growth performance of early-weaned piglets

Short Bowel Syndrome in Childhood

Epidermal growth factor and interleukin-1β synergistically stimulate the production of nitric oxide in rat intestinal epithelial cells

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