Growth Factors in the Gastrointestinal Tract

Barnard, J. A.; McHugh, Kirk M.

doi:10.1016/b978-012088394-3/50010-6

Cited by 4 publications

(3 citation statements)

References 954 publications

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“…This approach may appear counterintuitive, given the observation that both EGFR and PAR 2 are expressed basolaterally (3,30). However, evidence exists that they also are apically expressed (31). The fact that we have demonstrated that zonulin exerts a permeating effect, both in ex vivo and in vivo, when applied to the luminal aspect of the intestinal mucosa does not dispute the possibility that the protein acts basolaterally as well.…”

Section: Discussionmentioning

confidence: 62%

Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2

Tripathi¹,

Lammers²,

Goldblum³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

357

355

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Increased intestinal permeability (IP) has emerged recently as a common underlying mechanism in the pathogenesis of allergic, inflammatory, and autoimmune diseases. The characterization of zonulin, the only physiological mediator known to regulate IP reversibly, has remained elusive. Through proteomic analysis of human sera, we have now identified human zonulin as the precursor for haptoglobin-2 (pre-HP2). Although mature HP is known to scavenge free hemoglobin (Hb) to inhibit its oxidative activity, no function has ever been ascribed to its uncleaved precursor form. We found that the single-chain zonulin contains an EGF-like motif that leads to transactivation of EGF receptor (EGFR) via proteinase-activated receptor 2 (PAR 2) activation. Activation of these 2 receptors was coupled to increased IP. The siRNA-induced silencing of PAR 2 or the use of PAR 2 ؊/؊ mice prevented loss of barrier integrity. Proteolytic cleavage of zonulin into its ␣2-and ␤-subunits neutralized its ability to both activate EGFR and increase IP. Quantitative gene expression revealed that zonulin is overexpressed in the intestinal mucosa of subjects with celiac disease. To our knowledge, this is the initial example of a molecule that exerts a biological activity in its precursor form that is distinct from the function of its mature form. Our results therefore characterize zonulin as a previously undescribed ligand that engages a key signalosome involved in the pathogenesis of human immunemediated diseases that can be targeted for therapeutic interventions.autoimmune diseases ͉ epidermal growth factor receptor ͉ gut permeability ͉ proteinase-activated receptor 2 ͉ celiac disease

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Section: Discussionmentioning

confidence: 62%

Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2

Tripathi¹,

Lammers²,

Goldblum³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

357

355

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown that a number of growth factors, including EGF, TGF-α, trefoil growth peptides and bFGF, participate in the repair of tissue injury by stimulating cell proliferation and migration, an essential step for reepithelialization and ulcer healing (18,20,(22)(23)(24)(25). Gastric ulceration also induces the overexpression of EGF and its receptor EGFR (18,22).…”

Section: Discussionmentioning

confidence: 99%

Increased expression of epidermal growth factor receptor and betacellulin during the early stage of gastric ulcer healing

Choi

Park²,

Kim³

et al. 2008

Mol Med Report

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Epidermal growth factor receptor (EGFR) is important for the proliferation and differentiation of gastric mucosal cells. Betacellulin (BTC) is a novel ligand for EGFR Since their role is unclear in the ulcer healing process, we investigated their expression. Gastric ulcers in 30 Sprague-Dawley rats were induced by acetic acid. RT-PCR and Western blotting were performed to detect EGFR and BTC. Immunohistochemical studies were performed to detect EGFR, BTC and proliferating cell nuclear antigen (PCNA). The expression of EGFR and the BTC gene was significantly increased at 12 h, 24 h and 3 days after ulcer induction (P<0.05). The expression of EGFR and BTC protein was significantly increased at 24 h and 3 days and at 12 h, 24 h and 3 days after ulcer induction, respectively (P<0.05). The phosphorylation of EGFR also increased significantly and reached a maximum 24 h after ulcer induction (P<0.05). Immunostaining for EGFR and BTC was observed in numerous epithelial cells from the ulcer margin and ulcer bed, and corresponded to the localization of PCNA. To conclude, there was an increase in EGFR and BTC expression in the early stages of ulcer healing, localized in the epithelial cells of the ulcer margins and regenerating glands with proliferating activity. BTC/EGFR may play an important role in the early stages of ulcer healing.

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“…Persky et al, demonstrated that genetic attributions for eating behaviors were related to lower confidence in ability to control eating and weight (Persky et al, 2017). A meta-analysis study found that adolescents have difficulty in understanding the causes of obesity (Barnard and McHugh, 2006). In addition to their interactions with health-care providers, relationships with peers, and parents in the case of children, can also be responsible for the association between locus of control and obesity.…”

Section: Locus Of Controlmentioning

confidence: 99%

Behavioral Determinants of Obesity among Adolescents: A Qualitative Study

Kordasiabi¹,

Ramezani²,

Naghibi³

et al. 2022

JNFS

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Background: Overweight and obesity are the most serious public health challenges of developed and developing countries. The prevalence of childhood obesity has increased worldwide. This study aims to identify the behavioral determinants of overweight and obesity among adolescents. Methods: This is a qualitative study with directed approach to content analysis of in-depth semi-structured interviews. A total of 27 obese and overweight students (11girls, 16 boys) were recruited in this study based on the PRECEDE model (predisposing factor). The participants were recruited using a purposive sampling method to reach the maximum variation sampling. This sampling took over 6 months in 2018 at the Ghaemshahr middle school. Content analysis approach (directed) was used to analyze the interview. Results: Five main themes and 20 sub-themes of behavioral determinant were emerged from the interview. The main themes included perceived benefit, perceived threaten, self-efficacy, cues to action, and locus of control. The subthemes included self-empowerment, motivation and diligence role, enough information and parent pressure, long term benefits, physical health, doing favorite sports, perceived susceptibility and perceived severity, and internal and external locus of control. Conclusion: Self-efficacy and perceived benefit are the most significant determinants of preventive behavior in obese and overweight students; therefore, considering these variables in students can be applied in designing an interventional program that affect obesity preventive behaviors, increase parents’ awareness and school authorities.

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Growth Factors in the Gastrointestinal Tract

Cited by 4 publications

References 954 publications

Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2

Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2

Increased expression of epidermal growth factor receptor and betacellulin during the early stage of gastric ulcer healing

Behavioral Determinants of Obesity among Adolescents: A Qualitative Study

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