Epidermal growth factor promotes rapid response to epithelial injury in rabbit duodenum in vitro

Riegler, Martin; Sedivy, Roland; Sogukoglu, T; Cosentini, Enrico P.; Bischof, G.; Teleky, B.; Feil, W.; Schiessel, R; Hamilton, Gerhard; Wenzl, E.

doi:10.1053/gast.1996.v111.pm8698221

Cited by 58 publications

(46 citation statements)

References 3 publications

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“…Restitution is dependent on several factors present in vivo that are absent from our model system, including mucin-producing goblet cells, extracellular matrix producing fibroblasts, immune cells, and luminal contents. However, the IEC6, Caco2, and T84 model systems have been successful at predicting cellular mechanisms important in restitution in vivo (65)(66)(67).…”

Section: Discussionmentioning

confidence: 99%

CCR6 Regulation of the Actin Cytoskeleton Orchestrates Human Beta Defensin-2- and CCL20-mediated Restitution of Colonic Epithelial Cells

Vongsa

Zimmerman

Dwinell

2009

Journal of Biological Chemistry

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Intestinal inflammation is exacerbated by defects in the epithelial barrier and subsequent infiltration of microbes and toxins into the underlying mucosa. Production of chemokines and antimicrobial peptides by an intact epithelium provide the first line of defense against invading organisms. In addition to its antimicrobial actions, human beta defensin-2 (HBD2) may also stimulate the migration of dendritic cells through binding the chemokine receptor CCR6. As human colonic epithelium expresses CCR6, we investigated the potential of HBD2 to stimulate intestinal epithelial migration. Using polarized human intestinal Caco2 and T84 cells and non-transformed IEC6 cells, HBD2 was equipotent to CCL20 in stimulating migration. Neutralizing antibodies confirmed HBD2 and CCL20 engagement to CCR6 were sufficient to induce epithelial cell migration. Consistent with restitution, motogenic concentrations of HBD2 and CCL20 did not induce proliferation. Stimulation with those CCR6 ligands leads to calcium mobilization and elevated active RhoA, phosphorylated myosin light chain, and F-actin accumulation. HBD2 and CCL20 were unable to stimulate migration in the presence of either Rho-kinase or phosphoinositide 3-kinase inhibitors or an intracellular calcium chelator. Together, these data indicate that the canonical wound healing regulatory pathway, along with calcium mobilization, regulates CCR6-directed epithelial cell migration. These findings expand the mechanistic role for chemokines and HBD2 in mucosal inflammation to include immunocyte trafficking and killing of microbes with the concomitant activation of restitutive migration and barrier repair.

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Section: Discussionmentioning

confidence: 99%

CCR6 Regulation of the Actin Cytoskeleton Orchestrates Human Beta Defensin-2- and CCL20-mediated Restitution of Colonic Epithelial Cells

Vongsa

Zimmerman

Dwinell

2009

Journal of Biological Chemistry

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“…The high luminal EGF concentration makes for a steep concentration gradient from the lumen into the stroma (Gregory and Wilshire, 1975;Schaudies et al, 1989;Jorgensen et al, 1990;Nexo et al, 1992). This very high luminal EGF concentration may routinely serve in rapid repair of acute damage to a barrier as ligand (streaming across a wound in the epithelium) now interacts with basallateral epithelial receptors and receptors on stromal cells (Riegler et al, 1996). However, the existence of a focus of epithelial cells with chronically leaky tight junctions in the upper gastrointestinal tract or the lower urinary tract epithelial barrier would allow for long-term penetration of EGF into the stroma at these sites with cell kinetic effects on the epithelia as well as stromal fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

RasMutation Impairs Epithelial Barrier Function to a Wide Range of Nonelectrolytes

Mullin

Leatherman

Valenzano

et al. 2005

MBoC

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Although ras mutations have been shown to affect epithelial architecture and polarity, their role in altering tight junctions remains unclear. Transfection of a valine-12 mutated ras construct into LLC-PK 1 renal epithelia produces leakiness of tight junctions to certain types of solutes. Transepithelial permeability of D-mannitol increases sixfold but transepithelial electrical resistance increases >40%. This indicates decreased paracellular permeability to NaCl but increased permeability to nonelectrolytes. Permeability increases to D-mannitol (M r 182), polyethylene glycol (M r 4000), and 10,000-M r methylated dextran but not to 2,000,000-M r methylated dextran. This implies a "ceiling" on the size of solutes that can cross a ras-mutated epithelial barrier and therefore that the increased permeability is not due to loss of cells or junctions. Although the abundance of claudin-2 declined to undetectable levels in the ras-overexpressing cells compared with vector controls, levels of occludin and claudins 1, 4, and 7 increased. The abundance of claudins-3 and -5 remained unchanged. An increase in extracellular signal-regulated kinase-2 phosphorylation suggests that the downstream effects on the tight junction may be due to changes in the mitogen-activated protein kinase signaling pathway. These selective changes in permeability may influence tumorigenesis by the types of solutes now able to cross the epithelial barrier. INTRODUCTIONMutations in the three closely related ras genes, H-ras, K-ras, and N-ras, are among the most common mutations found in human cancer, reaching 50% in some types of tumors, such as colorectal carcinoma (Forrester et al., 1987;Andreyev et al., 1997Andreyev et al., , 1998Andreyev et al., , 2001). Vogelstein and colleagues have shown that mutations in K-ras occur early in the development of colon carcinomas (Vogelstein et al., 1988). This dominantly acting mutation in ras results in its constitutive activation and the subsequent triggering of its signaling pathway by influencing GTPase activity. It is clear that mutations in ras contribute both to the recurrence of the disease and to decreased survival (Andreyev et al., 1998). It is less clear, however, what the consequences of ras mutations are during the early stages of tumorigenesis. In this regard, one important issue is the effect of Ras activation on epithelial barrier function, perhaps the most basic of all epithelial functions, and a function shared by all epithelial tissues. Ras can exert fundamental effects on epithelial barrier function through the extracellular signal-regulated kinase-mitogen-activated protein (ERK-MAP) kinase pathway or through direct binding to the tight junction-associated protein, AF-6, which binds to ZO-1, which in turn links the tight junction to the actin cytoskeleton. Activated Ras is known to inhibit interaction between the tight junction-associated proteins, AF-6 and ZO-1, with resultant perturbation of intercellular junctions (Yamamoto et al., 1997). Modulation of tight junctions by G proteins in ge...

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“…EGFR exists in many species, including humans, cattle, pigs, dogs, mice, rats, and poultry, and the receptor in chickens recognizes human EGF (32,49,60,62,63). Previous studies have shown that EGF administration plays a protective role in a variety of intestinal insults by either reducing injury (4) or accelerating repair (7,21,51). Of particular interest to the context of this study is the finding that EGF can reduce colonization of the intestinal epithelium by enteropathogens (4)(5)(6).…”

mentioning

confidence: 92%

Epidermal Growth Factor Inhibits Campylobacter jejuni -Induced Claudin-4 Disruption, Loss of Epithelial Barrier Function, and Escherichia coli Translocation

et al. 2008

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Campylobacter jejuni is a leading cause of acute bacterial enteritis in humans. Poultry serves as a major reservoir of C. jejuni and is thought to act as a principal vehicle of transmission to humans. Epidermal growth factor (EGF) is a small amino acid peptide that exerts a broad range of activities on the intestinal epithelium. The aims of this study were to determine the effect of EGF on C. jejuni intestinal colonization in newly hatched chicks and to characterize its effects on C. jejuni-induced intestinal epithelial barrier disruption. White Leghorn chicks were treated with EGF daily, starting 1 day prior to C. jejuni infection, and were compared to control and C. jejuni-infected, EGF-treated chicks. Infected chicks shed C. jejuni in their feces throughout the study period. C. jejuni colonized the small intestine and cecum, disseminated to extraintestinal organs, and caused jejunal villus atrophy. EGF reduced jejunal colonization and dissemination of C. jejuni to the liver and spleen. In EGF-treated C. jejuni-infected chicks, villus height was not significantly different from that in untreated C. jejuni-infected chicks or controls. In vitro, C. jejuni attached to and invaded intestinal epithelial cells, disrupted tight junctional claudin-4, and increased transepithelial permeability. C. jejuni also promoted the translocation of noninvasive Escherichia coli C25. These C. jejuni-induced epithelial abnormalities were abolished by pretreatment with EGF, and the effect was dependent upon activation of the EGF receptor. These findings highlight EGF's ability to alter colonization of C. jejuni in the intestinal tract and to protect against pathogen-induced barrier defects.

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Epidermal growth factor promotes rapid response to epithelial injury in rabbit duodenum in vitro

Cited by 58 publications

References 3 publications

CCR6 Regulation of the Actin Cytoskeleton Orchestrates Human Beta Defensin-2- and CCL20-mediated Restitution of Colonic Epithelial Cells

CCR6 Regulation of the Actin Cytoskeleton Orchestrates Human Beta Defensin-2- and CCL20-mediated Restitution of Colonic Epithelial Cells

RasMutation Impairs Epithelial Barrier Function to a Wide Range of Nonelectrolytes

Epidermal Growth Factor Inhibits Campylobacter jejuni -Induced Claudin-4 Disruption, Loss of Epithelial Barrier Function, and Escherichia coli Translocation

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