The functional effects of nutrients on enterocyte proliferation and intestinal ion transport in early infancy

Buccigrossi, Vittoria; Giannattasio, Antonietta; Armellino, C.; Vecchio, Andrea Lo; Caiazzo, Maria Angela; Guarino, Alfredo

doi:10.1016/j.earlhumdev.2010.01.008

Cited by 16 publications

(8 citation statements)

References 29 publications

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“…In the intestinal epithelium, colonocytes undergo a switch from proliferation to differentiation. 18 , 19 Previous studies suggested that Zn 2+ promotes coloncytes differentiation, 20 but whether the ZnR/GPR39 may also promote this process is unknown. To study the role of ZnR/GPR39, early differentiation was induced in HT29 colonocytes by exposure to physiological concentrations of the short chain fatty acid butyrate (5 mM, 48 h).…”

Section: Resultsmentioning

confidence: 99%

“…Zinc is essential for intestinal epithelium renewal and is directly involved in crypt cell proliferation 30 and epithelial intestinal cell differentiation, 20 whereas zinc deficiency is associated with suppression of colonocyte proliferation. 20 Moreover, many studies underscored the importance of extracellular Zn 2+ in cellular signaling associated with proliferation of colonocytes. For example, Zn 2+ was linked to regulation of the MAPK pathway, 31 , 32 and was also reported to activate the PI3 pathway.…”

Section: Discussionmentioning

confidence: 99%

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The zinc sensing receptor, ZnR/GPR39, controls proliferation and differentiation of colonocytes and thereby tight junction formation in the colon

2014

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The intestinal epithelium is a renewable tissue that requires precise balance between proliferation and differentiation, an essential process for the formation of a tightly sealed barrier. Zinc deficiency impairs the integrity of the intestinal epithelial barrier and is associated with ulcerative and diarrheal pathologies, but the mechanisms underlying the role of Zn2+ are not well understood. Here, we determined a role of the colonocytic Zn2+ sensing receptor, ZnR/GPR39, in mediating Zn2+-dependent signaling and regulating the proliferation and differentiation of colonocytes. Silencing of ZnR/GPR39 expression attenuated Zn2+-dependent activation of ERK1/2 and AKT as well as downstream activation of mTOR/p70S6K, pathways that are linked with proliferation. Consistently, ZnR/GPR39 silencing inhibited HT29 and Caco-2 colonocyte proliferation, while not inducing caspase-3 cleavage. Remarkably, in differentiating HT29 colonocytes, silencing of ZnR/GPR39 expression inhibited alkaline phosphatase activity, a marker of differentiation. Furthermore, Caco-2 colonocytes showed elevated expression of ZnR/GPR39 during differentiation, whereas silencing of ZnR/GPR39 decreased monolayer transepithelial electrical resistance, suggesting compromised barrier formation. Indeed, silencing of ZnR/GPR39 or chelation of Zn2+ by the cell impermeable chelator CaEDTA was followed by impaired expression of the junctional proteins, that is, occludin, zonula-1 (ZO-1) and E-cadherin. Importantly, colon tissues of GPR39 knockout mice also showed a decrease in expression levels of ZO-1 and occludin compared with wildtype mice. Altogether, our results indicate that ZnR/GPR39 has a dual role in promoting proliferation of colonocytes and in controlling their differentiation. The latter is followed by ZnR/GPR39-dependent expression of tight junctional proteins, thereby leading to formation of a sealed intestinal epithelial barrier. Thus, ZnR/GPR39 may be a therapeutic target for promoting epithelial function and tight junction barrier integrity during ulcerative colon diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The zinc sensing receptor, ZnR/GPR39, controls proliferation and differentiation of colonocytes and thereby tight junction formation in the colon

2014

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“…This finding could be attributable to the numerous positive activities of zinc at the intestinal level. These include regulation of intestinal permeability, epithelial cell growth and differentiation, and immune response (9,22). The mechanisms of action of zinc were not investigated in this trial.…”

Section: Discussionmentioning

confidence: 99%

Zinc supplementation reduces morbidity and mortality in very-low-birth-weight preterm neonates: a hospital-based randomized, placebo-controlled trial in an industrialized country

Terrin¹,

Canani²,

Passariello³

et al. 2013

The American Journal of Clinical Nutrition

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Background: Zinc plays a pivotal role in the pathogenesis of many diseases and in body growth. Preterm neonates have high zinc requirements. Objective: The objective of the study was to investigate the efficacy of zinc supplementation in reducing morbidity and mortality in preterm neonates and to promote growth. Design: This was a prospective, double-blind, randomized controlled study of very-low-birth-weight preterm neonates randomly allocated on the seventh day of life to receive (zinc group) or not receive (control group) oral zinc supplementation. Total prescribed zinc intake ranged from 9.7 to 10.7 mg/d in the zinc group and from 1.3 to 1.4 mg/d in the placebo control group. The main endpoint was the rate of neonates with $1 of the following morbidities: lateonset sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular leucomalacia, and retinopathy of prematurity. Secondary outcomes were mortality and body growth. Results: We enrolled 97 neonates in the zinc group and 96 in the control group. Morbidities were significantly lower in the zinc group (26.8% compared with 41.7%; P = 0.030). The occurrence of necrotizing enterocolitis was significantly higher in the control group (6.3% compared with 0%; P = 0.014). Mortality risk was higher in the placebo control group (RR: 2.37; 95% CI: 1.08, 5.18; P = 0.006). Daily weight gain was similar in the zinc (18.2 6 5.6 g $ kg 21 $ d 21 ) and control (17.0 6 8.7 g $ kg 21 $ d 21

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“…The modulation of intestinal functions by nutrients is exerted in part through a direct interaction between a single nutrient and the enterocytes (Buccigrossi et al 2010). MI was shown to be responsible for in vitro growth of human oocytes (Papaleo et al 2009).…”

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confidence: 99%

Effects ofmyo-inositol on proliferation, differentiation, oxidative status and antioxidant capacity of carp enterocytes in primary culture

et al. 2012

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This study investigated the effects of myo‐inositol (MI) on the growth and antioxidant capacity of carp enterocytes. The enterocytes were incubated in media containing 0, 15, 30, 45, 60 and 75 mg MI L−1 for 96 h. The results indicated that MI could increase cell viability. In addition, the activities of cellular alkaline phosphatase (AKP), gamma‐glutamyl transpeptidase (γ‐GT), Na+, K+‐adenosine trisphosphatase (Na+, K+‐ATPase) and creatinkinase (CK) increased with MI supplementation at levels ranging from 15 to 60 mg MI L−1 medium, indicating an improvement in cell differentiation and function. Further, enzymatic antioxidant ability, as measured by total superoxide dismutase (T‐SOD), Cu/Zn‐SOD, Mn‐SOD, catalase (CAT), glutathione peroxidase (GPx) and glutathione‐S‐transferase (GST) activities, improved with MI supplementation. Finally, cell damage, as indicated by lactic acid dehydrogenase (LDH) activity, malondialdehyde (MDA) content of the medium and cellular protein carbonyls (PC), was all depressed by MI. Correlation analyses showed that cell viability (MTT) was positively related to the antioxidant enzyme activities, but negatively related to cell damage (LDH, MDA and PC). In summary, the data showed that MI could improve the growth of fish enterocytes. This result may be partly due to the enhanced antioxidant status and depressed oxidative damage.

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The functional effects of nutrients on enterocyte proliferation and intestinal ion transport in early infancy

Cited by 16 publications

References 29 publications

The zinc sensing receptor, ZnR/GPR39, controls proliferation and differentiation of colonocytes and thereby tight junction formation in the colon

The zinc sensing receptor, ZnR/GPR39, controls proliferation and differentiation of colonocytes and thereby tight junction formation in the colon

Zinc supplementation reduces morbidity and mortality in very-low-birth-weight preterm neonates: a hospital-based randomized, placebo-controlled trial in an industrialized country

Effects ofmyo-inositol on proliferation, differentiation, oxidative status and antioxidant capacity of carp enterocytes in primary culture

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