Role of the GLP2–Wnt1 axis in silicon-rich alkaline mineral water maintaining intestinal epithelium regeneration in piglets under early-life stress

Stress-induced intestinal epithelial injury (IEI) and a delay in repair in infancy are predisposing factors for refractory gut diseases in adulthood, such as irritable bowel syndrome (IBS). Hence, it is necessary to develop appropriate mitigation methods for mammals when experiencing early-life stre...

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Veröffentlicht in:Cellular and molecular life sciences : CMLS 2024-12, Vol.81 (1), p.126-126, Article 126
Hauptverfasser: Chen, Jian, Dai, Xue-Yan, Zhao, Bi-Chen, Xu, Xiang-Wen, Kang, Jian-Xun, Xu, Ya-Ru, Li, Jin-Long
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container_title Cellular and molecular life sciences : CMLS
container_volume 81
creator Chen, Jian
Dai, Xue-Yan
Zhao, Bi-Chen
Xu, Xiang-Wen
Kang, Jian-Xun
Xu, Ya-Ru
Li, Jin-Long
description Stress-induced intestinal epithelial injury (IEI) and a delay in repair in infancy are predisposing factors for refractory gut diseases in adulthood, such as irritable bowel syndrome (IBS). Hence, it is necessary to develop appropriate mitigation methods for mammals when experiencing early-life stress (ELS). Weaning, as we all know, is a vital procedure that all mammalian newborns, including humans, must go through. Maternal separation (MS) stress in infancy (regarded as weaning stress in animal science) is a commonly used ELS paradigm. Drinking silicon-rich alkaline mineral water (AMW) has a therapeutic effect on enteric disease, but the specific mechanisms involved have not been reported. Herein, we discover the molecular mechanism by which silicon-rich AMW repairs ELS-induced IEI by maintaining intestinal stem cell (ISC) proliferation and differentiation through the glucagon-like peptide (GLP)2–Wnt1 axis. Mechanistic study showed that silicon-rich AMW activates GLP2-dependent Wnt1/β-catenin pathway, and drives ISC proliferation and differentiation by stimulating Lgr5 + ISC cell cycle passage through the G1–S-phase checkpoint, thereby maintaining intestinal epithelial regeneration and IEI repair. Using GLP2 antagonists (GLP2 3−33 ) and small interfering RNA (SiWnt1) in vitro, we found that the GLP2–Wnt1 axis is the target of silicon-rich AMW to promote intestinal epithelium regeneration. Therefore, silicon-rich AMW maintains intestinal epithelium regeneration through the GLP2–Wnt1 axis in piglets under ELS. Our research contributes to understanding the mechanism of silicon-rich AMW promoting gut epithelial regeneration and provides a new strategy for the alleviation of ELS-induced IEI.
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Mechanistic study showed that silicon-rich AMW activates GLP2-dependent Wnt1/β-catenin pathway, and drives ISC proliferation and differentiation by stimulating Lgr5 + ISC cell cycle passage through the G1–S-phase checkpoint, thereby maintaining intestinal epithelial regeneration and IEI repair. Using GLP2 antagonists (GLP2 3−33 ) and small interfering RNA (SiWnt1) in vitro, we found that the GLP2–Wnt1 axis is the target of silicon-rich AMW to promote intestinal epithelium regeneration. Therefore, silicon-rich AMW maintains intestinal epithelium regeneration through the GLP2–Wnt1 axis in piglets under ELS. 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Mechanistic study showed that silicon-rich AMW activates GLP2-dependent Wnt1/β-catenin pathway, and drives ISC proliferation and differentiation by stimulating Lgr5 + ISC cell cycle passage through the G1–S-phase checkpoint, thereby maintaining intestinal epithelial regeneration and IEI repair. Using GLP2 antagonists (GLP2 3−33 ) and small interfering RNA (SiWnt1) in vitro, we found that the GLP2–Wnt1 axis is the target of silicon-rich AMW to promote intestinal epithelium regeneration. Therefore, silicon-rich AMW maintains intestinal epithelium regeneration through the GLP2–Wnt1 axis in piglets under ELS. 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Mol. Life Sci</stitle><addtitle>Cell Mol Life Sci</addtitle><date>2024-12-01</date><risdate>2024</risdate><volume>81</volume><issue>1</issue><spage>126</spage><epage>126</epage><pages>126-126</pages><artnum>126</artnum><issn>1420-682X</issn><eissn>1420-9071</eissn><abstract>Stress-induced intestinal epithelial injury (IEI) and a delay in repair in infancy are predisposing factors for refractory gut diseases in adulthood, such as irritable bowel syndrome (IBS). Hence, it is necessary to develop appropriate mitigation methods for mammals when experiencing early-life stress (ELS). Weaning, as we all know, is a vital procedure that all mammalian newborns, including humans, must go through. Maternal separation (MS) stress in infancy (regarded as weaning stress in animal science) is a commonly used ELS paradigm. Drinking silicon-rich alkaline mineral water (AMW) has a therapeutic effect on enteric disease, but the specific mechanisms involved have not been reported. Herein, we discover the molecular mechanism by which silicon-rich AMW repairs ELS-induced IEI by maintaining intestinal stem cell (ISC) proliferation and differentiation through the glucagon-like peptide (GLP)2–Wnt1 axis. Mechanistic study showed that silicon-rich AMW activates GLP2-dependent Wnt1/β-catenin pathway, and drives ISC proliferation and differentiation by stimulating Lgr5 + ISC cell cycle passage through the G1–S-phase checkpoint, thereby maintaining intestinal epithelial regeneration and IEI repair. Using GLP2 antagonists (GLP2 3−33 ) and small interfering RNA (SiWnt1) in vitro, we found that the GLP2–Wnt1 axis is the target of silicon-rich AMW to promote intestinal epithelium regeneration. Therefore, silicon-rich AMW maintains intestinal epithelium regeneration through the GLP2–Wnt1 axis in piglets under ELS. 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subjects Antagonists
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cell cycle
Cell differentiation
Differentiation
Digestive system
Drinking water
Epithelium
Gastrointestinal tract
Glucagon
Intestine
Irritable bowel syndrome
Life Sciences
Mammals
Mineral water
Molecular modelling
Neonates
Original
Original Article
Regeneration
Silicon
siRNA
Stem cells
Swine
Weaning
β-Catenin
title Role of the GLP2–Wnt1 axis in silicon-rich alkaline mineral water maintaining intestinal epithelium regeneration in piglets under early-life stress
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