Enteral Absorption of Erythropoietin in the Suckling Rat

Miller-Gilbert, Amy L; Dubuque, Suzanne H.; Dvořák, Bohuslav; Williams, Catherine S.; Grille, James G.; Woodward, S.; Koldovský, Otakar; Kling, Pamela J.

doi:10.1203/00006450-200108000-00016

Cited by 20 publications

(31 citation statements)

References 38 publications

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“…If milk-borne Epo is absorbed enterally, stimulating vessel growth in the immature digestive tract, the risk for local tissue hypoxia may be lessened. We have shown that a relatively high percentage of rhEpo remains in the wall and vascular bundle of the small intestine after enteral administration (11), but thus far, the precise biologic effects of milk-borne Epo have not been identified.…”

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confidence: 97%

Erythropoietin Stimulates Vasculogenesis in Neonatal Rat Mesenteric Microvascular Endothelial Cells

et al. 2002

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Human breast milk is a rich source of growth factors, including erythropoietin (Epo), the endogenous hormonal stimulant of erythropoiesis. Recombinant human Epo (rhEpo) has been shown to stimulate 1) angiogenesis, the process of new blood vessel growth from preexisting vessels; 2) vasculogenesis, tubule formation from single-cell suspensions; and 3) endothelial cell proliferation in immortalized endothelial cells and vessel explants. We hypothesized that Epo would induce mitogenesis and stimulate vasculogenesis in primary cultures of microvascular endothelial cells (MVECs) from neonatal rat mesentery. Isolation, purification, characterization, and culture of MVECs were performed. Cell proliferative effects of rhEpo were studied by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in cultured MVECs. Vasculogenic effects of rhEpo were examined on cultured MVECs plated on either hormone-rich Matrigel substratum or the extracellular matrix protein, type I collagen. Our findings show that MVECs are isolated and purified, and that rhEpo stimulates MVEC proliferation, with maximal proliferation seen with a concentration of 50 IU/mL rhEpo. Tubule formation assays reveal that an rhEpo concentration of 50 IU/mL produces maximal tubule formation after 12 h on both Matrigel and the simple substratum, type I collagen. Our study is the first to examine the effects of rhEpo on the endothelium of the neonatal gastrointestinal tract. These data suggest that Epo may have a trophic effect on the vasculature of the gastrointestinal tract early in development. Furthermore, as Epo has been measured in breast milk, and its receptor has been shown to exist on the mucosa and gastrointestinal vasculature, Epo may be an endogenous stimulant of vessel growth during neonatal gastrointestinal development. Many growth factors and hematopoietic cytokines have been measured in human breast milk (1-4). Epo, the primary hormonal stimulant of red blood cell production, is among this group of substances (5). As it does for other growth factors, human milk protects Epo from proteolytic degradation (5). The EpoR is present in the brush border and vascular endothelium of the mucosa lining the small intestine (6). Because endothelial cells and erythropoietic cells are derived from the same progenitor cell, the hemangioblast, it is possible that Epo exerts similar trophic effects on endothelium as it does on erythropoietic cells (7). Milk-borne Epo has been shown to be absorbed without degradation (6). These data suggest that Epo may act as a stimulator of normal development of the digestive tract.Among its many potential effects, Epo may stimulate angiogenesis, the process by which preexisting blood vessels give rise to new vessels. During angiogenesis, proteins from vascular endothelial cells degrade the extracellular matrix, migrate into perivascular space, proliferate, align themselves into tu- ABSTRACT472

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confidence: 97%

Erythropoietin Stimulates Vasculogenesis in Neonatal Rat Mesenteric Microvascular Endothelial Cells

et al. 2002

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“…After enteral 125 I-rhEpo dosing, Miller-Gilbert et al (8) observed that intact 125 I-rhEpo was found in gastric and small intestinal walls and lumens. Juul et al (34) found that among rEpo treated pups, 1) the small bowel was longer, 2) the intestinal villus surface areas was larger in a dose-dependent manner, and 3) BrdU uptake was greater.…”

Section: Discussionmentioning

confidence: 99%

“…Growth factors are involved in this regulation (1,2), and among those factors studied are epidermal growth factor (EGF), insulin-like growth factor (IGF), erythropoietin (Epo), and transforming growth factor (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”

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Effects of Enterally Administering Granulocyte Colony-Stimulating Factor to Suckling Mice

2004

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“…Human milk contains numerous growth modulators [41,45,46] [66][67][68], and granulocyte colony-stimulating factor (CSF) [69], to name but a few. What amniotic fluid and human milk share, then, is bioactivity, the capacity to stimulate cells to grow or undergo reparative processes [36,70].…”

Section: Transitioning From Amniotic Fluid To Human Milkmentioning

confidence: 99%

Host Factors in Amniotic Fluid and Breast Milk that Contribute to Gut Maturation

Wagner

Taylor

Johnson

2007

Clinic Rev Allerg Immunol

150

103

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The gut represents a complex organ system with regional differences, which reflect selective digestive and absorptive functions that change constantly in response to bodily requirements and the outside milieu. As a barrier to the external environment, gut epithelium must be renewed rapidly and repeatedly. Growth and renewal of gut epithelial cells is dependent on controlled cell stimulation and proliferation by a number of signaling processes and agents, including gut peptides-both endogenous and exogenous sources. This cascade of events begins during fetal development; with the ingestion of amniotic fluid, this process is enhanced and continued during infancy and early childhood through the ingestion of human milk. Events influenced by amniotic fluid during fetal development and those influenced by human milk that unfold after birth and early childhood to render the gut mature are presented.

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Enteral Absorption of Erythropoietin in the Suckling Rat

Cited by 20 publications

References 38 publications

Erythropoietin Stimulates Vasculogenesis in Neonatal Rat Mesenteric Microvascular Endothelial Cells

Erythropoietin Stimulates Vasculogenesis in Neonatal Rat Mesenteric Microvascular Endothelial Cells

Effects of Enterally Administering Granulocyte Colony-Stimulating Factor to Suckling Mice

Host Factors in Amniotic Fluid and Breast Milk that Contribute to Gut Maturation

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