Intravenous Epidermal Growth Factor/Urogastrone Increases Small-Intestinal Cell Proliferation in Congenital Microvillous Atrophy

Walker-Smith, J A; Phillips, Alan D.; Walford, Norman; Gregory, H.; Fitzgerald, J. D.; Maccullagh, K.; Wright, Nicholas

doi:10.1016/s0140-6736(85)90762-7

Cited by 118 publications

(44 citation statements)

References 8 publications

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“…In the human fetal jejunum and colon, EGF stimulates proliferation and differentiation (1 7, 18). EGF also promotes proliferation of the small intestinal mucosa in neonatal microvillous atrophy (48). The present demonstration of expression of both TGF-a and EGF in the human fetal GI tract further implies an important role for these peptides in the developing gut.…”

Section: Discussionsupporting

confidence: 58%

Transforming Growth Factor-α and Epidermal Growth Factor Expression in Human Fetal Gastrointestinal Tract

Miettinen

1993

Pediatr Res

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ABSTRACT. Epidermal growth factor (EGF) and trans-found in human fetal (6, 11) and adult (12) intestine. In fetal forming growth factor-a (TGF-a) are mitogenic to the rhesus monkey (13) and suckling rabbits (14), EGF stimulates intestinal epithelium. To further clarify their role in the proliferation of the intestinal epithelium. However, in fetal mice developing human fetal gut, their expression was studied (15) and newborn rats (16), it has no effect on DNA synthesis. in fetuses at 15 to 20 wk of gestation. TGF-a mRNA was Therefore, the effects of EGF on small intestinal cell proliferation present throughout the gastrointestinal tract, most abun-and maturation seem to vary with the developmental stage (17). dantly in the duodenum. EGF mRNA could be detected In cultured human fetal jejunal explants, EGF increases lactase only with ribonuclease protection assay and reverse tran-production and decreases DNA synthesis (17). DNA synthesis is scription-polymerase chain reaction analysis. The effect of also diminished by EGF in human fetal colon explants (18). EGF and TGF-a on TGF-a mRNA expression was studied EGF-R binds both EGF and TGF-a. Binding studies with 1251-by culturing explants of fetal jejunum, ileum, and colon for EGF show that in the human fetus EGF-R is present in the 7 d in Leibowitz L-15 medium supplemented with 100 pg/ epithelial cells of both the small intestine and colon from the L of either EGF or TGF-a. EGF receptor-like immuno-12th wk of gestation (19). Immunoreactive EGF-R is detectable reactivity was detected in both the villi and the crypts. In in the villous epithelial cells from the 16th wk of gestation (20). the jejunum, exogenous EGF up-regulated TGF-a mRNA EGF up-regulates TGF-a mRNA in human colon carcinoma 3-fold. However, exogenous TGF-a reduced its own mRNA (2 1) and in rat intestinal epithelial cell lines (22) during 2 to 48 by 40%. No mature 6-kD TGF-a was detected in the h of exposure. However, for a study of intestinal development, a culture medium by Western blotting, but precursor forms longer stimulation time is needed to mimic the in vivo situation of approximately 30 and 68 kD were present. The ileum in utero with continuous passage of amniotic fluid through the and colon did not respond to either growth factor. Besides fetal gut. The present study was undertaken to clarify the expresthe gut, TGF-a was expressed in the gallbladder, salivary sion and role of EGF and TGF-a in the developing human fetal gland, adrenals, brain, kidney, liver, and placenta. The data GI tract. It also explores whether these peptides regulate TGF-a imply an important role for TGF-a and EGF in the devel-mRNA production in long-term organ explant cultures. oping intestine. (Pediatr Res 33: 481-486, 1993) MATERIALS AND METHODS AbbreviationsFetal tissues. Tissues were obtained from prostaglandin-in-EGF, epidermal growth factor duced legal abortions at 15 to 20 wk of gestation. The study was EGF-R, epidermal growth factor receptor approved by the Ethical Committee of the Hospital. Delay from GI, gas...

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Section: Discussionsupporting

confidence: 58%

Transforming Growth Factor-α and Epidermal Growth Factor Expression in Human Fetal Gastrointestinal Tract

Miettinen

1993

Pediatr Res

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“…Intravenous epidermal growth factor increased the small intestinal cell proliferation in a patient with congenital microvillous atrophy [33], and subcutaneously administered granulocyte colony-stimulating factor was used to treat fistulas in a patient with Crohn's disease, in whom standard treatments had failed [34]. Subcutaneous administration of interleukin-10 was used with variable outcomes in a small number of adults with refractory celiac disease [35].…”

Section: Discussionmentioning

confidence: 99%

Abnormal Intestinal Histology in Neonates with Congenital Anomalies of the Gastrointestinal Tract

Condino

Barleycorn

et al. 2004

Neonatology

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In animal models, when swallowing is experimentally prevented in utero, bowel length and weight are reduced, and villus height, crypt depth, and villus function are retarded. Little is known about the intestinal histology in infants with gastrointestinal (GI) tract anomalies. We examined the histological architecture of the intestine in neonates with GI anomalies in comparison to that of normal fetuses. Villus height, area, and length and crypt depth of normal fetuses were quantified in the proximal small bowel (n = 11) and measurements compared to those of surgical specimens of neonates with congenital anomalies of the GI tract (n = 16). Villus height and area and lamina propria height and area increased linearly from 8 to 24 weeks of gestation. In infants with anomalies of the GI tract, the villi were blunted and lacked normal histological architecture, the crypts were disorganized, and the crypt depth was significantly decreased (p = 0.004). Enterocyte height and area were significantly greater in neonates with congenital anomalies of the GI tract. The intestinal histology in neonates with congenital anomalies of the GI tract differs significantly from that of normal fetuses.

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“…Thus, EGF ligands might be useful for preterm infants. Indeed, EGF has been used incidentally in congenital microvillus atrophy (32), prevention of NEC (33), and pediatric short bowel syndrome (30). Association of EGF-R signaling to carcinogenesis has prevented routine EGF substitution.…”

Section: Discussionmentioning

confidence: 99%

Hydrocortisone and Indomethacin Negatively Modulate EGF-R Signaling in Human Fetal Intestine

et al. 2007

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Concomitant use of hydrocortisone and the nonspecific cyclo-oxygenase (COX)-inhibitor indomethacin increases the risk for intestinal perforations in preterm infants. We determined whether this was associated with insufficient epidermal growth factor receptor (EGF-R) signaling. We tested the effect of EGF, hydrocortisone, and indomethacin on its activation, cell proliferation and migration, COX-2 expression, and prostaglandin E 2 (PGE 2 ) production. Human small intestine epithelial cell line FHsInt74 and EGF-Rdeficient mice [EGF-R (-/-)] were used as models. The data revealed that EGF-R signaling had a bimodal positive effect on fetal enterocyte: 1) it increased cell proliferation and migration synergistically with hydrocortisone and 2) up-regulated COX-2 mRNA expression and subsequent PGE 2 production. Correlating with this, COX-2 protein expression was down-regulated in EGF-R (-/-) intestine. Despite a positive effect on cell proliferation with EGF, hydrocortisone blunted the stimulatory effect of EGF on COX-2 expression and PGE 2 production. Addition of indomethacin even further inhibited the EGF-stimulated PGE 2 synthesis. The data suggest that concomitant use of indomethacin and hydrocortisone on preterm infants, who physiologically synthesize only low levels of EGF-R ligands, may lead to intestinal problems related to failure in cytoprotective and regenerative events.

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Intravenous Epidermal Growth Factor/Urogastrone Increases Small-Intestinal Cell Proliferation in Congenital Microvillous Atrophy

Cited by 118 publications

References 8 publications

Transforming Growth Factor-α and Epidermal Growth Factor Expression in Human Fetal Gastrointestinal Tract

Transforming Growth Factor-α and Epidermal Growth Factor Expression in Human Fetal Gastrointestinal Tract

Abnormal Intestinal Histology in Neonates with Congenital Anomalies of the Gastrointestinal Tract

Hydrocortisone and Indomethacin Negatively Modulate EGF-R Signaling in Human Fetal Intestine

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