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Current Protein & Peptide Science


ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Review Article

Differentiation and Proliferation of Intestinal Stem Cells and its Underlying Regulated Mechanisms during Weaning

Author(s): Xi Chen, Zehong Yang, Huiling Hu, Wentao Duan, Aiping Wang, Yanbin Dong, Weihang Gao, Song Deng, Bo Cheng, Jiali Li, Nannan Sun, Zhibin Cheng*, Wenfeng Guo*, Yanwu Li* and Yong Gao*

Volume 20 , Issue 7 , 2019

Page: [690 - 695] Pages: 6

DOI: 10.2174/1389203720666190125101834

Price: $65


Weaning is a stressful event associated with gastrointestinal disorders and increased disease susceptibility. Many studies have reported the changes that happened in the gut of various mammals such as pigs and rats after weaning. These findings suggest that the development of intestinal tract mainly is affected at the time of weaning through interfering in the differentiation and proliferation of intestinal stem cells. Weaning stress stimulates the rapid differentiation and proliferation of intestinal stem cells in order to adjust to changes caused by weaning, which are mainly manifested as deeper crypt depth and decreased intestine villus height. However, the accelerated cellular process may lead to an increase in the proportion of immature intestinal epithelial cells and goblet cells, which affect intestinal permeability and reduce the gut-barrier function against toxins and pathogens. This review briefly describes the effects coforticotrophin-releasing factor (CRF), epidermal growth factor (EGF) and polyamines on the differentiation and proliferation of intestinal stem cells after weaning and discusses its possible underlying regulatory mechanisms. Firstly, weaning stress activates CRF to binds its receptors, which induces proinflammatory responses and promote rapid differentiation and proliferation of intestinal stem cells to a larger fraction of immature intestinal epithelial cells and goblet cells. Secondly, the lack of EGF after weaning inhibits the expression of goblet cell maturation factors and makes it difficult for goblet cells and intestinal epithelial cells to mature. Finally, diet and endogenous synthesis lead to excessive polyamines in the intestine, which promote the proliferation of intestinal stem cells by regulating the expression of human antigen R (HuR) and other related genes at the time of weaning.

Keywords: Intestinal stem cells, weaning, corticotrophin-releasing factor (CRF), epidermal growth factor (EGF), polyamines, mammals.

Graphical Abstract
Moeser, A.J.; Klok, C.V.; Ryan, K.A.; Wooten, J.G.; Little, D.; Cook, V.L.; Blikslager, A.T. Stress signaling pathways activated by weaning mediate intestinal dysfunction in the pig. Am. J. Physiol- Gastr. L. 2007. 292, G173-G181.
van Beers-Schreurs, H.M.; Nabuurs, M.J.; Vellenga, L.; Kalsbeek-van der Valk, H.J.; Wensing, T.; Breukink, H.J. Weaning and the weanling diet influence the villous height and crypt depth in the small intestine of pigs and alter the concentrations of short-chain fatty acids in the large intestine and blood. J. Nutr., 1998, 128, 947-953.
Yang, H.; Xiong, X.; Wang, X.; Tan, B.; Li, T.; Yin, Y. Effects of weaning on intestinal upper villus epithelial cells of piglets. PLoS One, 2016, 11e0150216
Barker, N.; van de Wetering, M.; Clevers, H. The intestinal stem cell. Genes Dev., 2008, 22, 1856-1864.
Jones, B.A.; Gores, G.J. Physiology and pathophysiology of apoptosis in epithelial cells of the liver, pancreas, and intestine. Am. J. Physiol., 1997, 273, G1174-G1188.
Deplancke, B.; Gaskins, H.R. Microbial modulation of innate defense: Goblet cells and the intestinal mucus layer. Am. J. Clin. Nutr., 2001, 73, 1131S-1141S.
Fontaine, N.; Meslin, J.C.; Dore, J. Selective in vitro degradation of the sialylated fraction of germ-free rat mucins by the caecal flora of the rat. Reprod. Nutr. Dev., 1998, 38, 289-296.
Koninkx, J.F.; Mirck, M.H.; Hendriks, H.G.; Mouwen, J.M.; van Dijk, J.E. Nippostrongylus brasiliensis: histochemical changes in the composition of mucins in goblet cells during infection in rats. Exp. Parasitol., 1988, 65, 84-90.
Montagne, L.; Boudry, G.; Favier, C.; Le Huerou-Luron, I.; Lalles, J.P.; Seve, B. Main intestinal markers associated with the changes in gut architecture and function in piglets after weaning. Br. J. Nutr., 2007, 97, 45-57.
Brown, P.J.; Miller, B.G.; Stokes, C.R.; Blazquez, N.B.; Bourne, F.J. Histochemistry of mucins of pig intestinal secretory epithelial cells before and after weaning. J. Comp. Pathol., 1988, 98, 313-323.
Lopez-Pedrosa, J.M.; Torres, M.I.; Fernandez, M.I.; Rios, A.; Gil, A. Severe malnutrition alters lipid composition and fatty acid profile of small intestine in newborn piglets. J. Nutr., 1998, 128, 224-233.
Boyle, J.T.; Koldovsky, O. Critical role of adrenal glands in precocious increase in jejunal sucrase activity following premature weaning in rats: Negligible effect of food intake. J. Nutr., 1980, 110, 169-177.
Cummins, A.G.; Thompson, F.M. Effect of breast milk and weaning on epithelial growth of the small intestine in humans. Gut, 2002, 51, 748-754.
Henning, S.J. Biochemistry of intestinal development. Environ. Health Perspect., 1979, 33, 9-16.
Bale, T.L.; Vale, W.W. CRF, and CRF receptors: role in stress responsivity and other behaviors. Annu. Rev. Pharmacol. Toxicol., 2004, 44, 525-557.
Hu, C.H.; Qian, Z.C.; Song, J.; Luan, Z.S.; Zuo, A.Y. Effects of zinc oxide-montmorillonite hybrid on growth performance, intestinal structure, and function of broiler chicken. Poult. Sci., 2013, 92, 143-150.
Upton, G.V.; Amatruda, T.T. Jr. Evidence for the presence of tumor peptides with corticotropin-releasing-factor-like activity in the ectopic ACTH syndrome. N. Engl. J. Med., 1971, 285, 419-424.
Xiong, X.; Yang, H.; Tan, B.; Yang, C.; Wu, M.; Liu, G.; Kim, S.W.; Li, T.; Li, L.; Wang, J.; Wu, G.; Yin, Y. Differential expression of proteins involved in energy production along the crypt-villus axis in early-weaning pig small intestine. Am. J. Physiol-Gastr L., 2015, 309, G229-G237.
Hedemann, M.S.; Hojsgaard, S.; Jensen, B.B. Small intestinal morphology and activity of intestinal peptidases in piglets around weaning. J. Anim. Physiol. Anim. Nutr. (Berl.), 2003, 87, 32-41.
Labus, J.S.; Hubbard, C.S.; Bueller, J.; Ebrat, B.; Tillisch, K.; Chen, M.; Stains, J.; Dukes, G.E.; Kelleher, D.L.; Naliboff, B.D.; Fanselow, M.; Mayer, E.A. Impaired emotional learning and involvement of the corticotropin-releasing factor signaling system in patients with irritable bowel syndrome., Gastroenterology,. 2013. 145, 1253-1261 e1-3.
Schneider, M.R.; Wolf, E. The epidermal growth factor receptor ligands at a glance. J. Cell. Physiol., 2009, 218, 460-466.
James, P.S.; Smith, M.W.; Tivey, D.R.; Wilson, T.J. Epidermal growth factor selectively increases maltase and sucrase activities in neonatal piglet intestine. J. Physiol., 1987, 393, 583-594.
Bedford, A.; Huynh, E.; Fu, M.; Zhu, C.; Wey, D.; de Lange, C.; Li, J. Growth performance of early-weaned pigs is enhanced by feeding epidermal growth factor-expressing Lactococcus lactis fermentation product. J. Biotechnol., 2014, 173, 47-52.
Zou, T.; Mazan-Mamczarz, K.; Rao, J.N.; Liu, L.; Marasa, B.S.; Zhang, A.H.; Xiao, L.; Pullmann, R.; Gorospe, M.; Wang, J.Y. Polyamine depletion increases cytoplasmic levels of RNA-binding protein HuR leading to stabilization of nucleophosmin and p53 mRNAs. J. Biol. Chem., 2006, 281, 19387-19394.
Larque, E.; Sabater-Molina, M.; Zamora, S. Biological significance of dietary polyamines. Nutrition, 2007, 23, 87-95.
Wu, G.; Flynn, N.E.; Knabe, D.A. Enhanced intestinal synthesis of polyamines from proline in cortisol-treated piglets. Am. J. Physiol. Endocrinol. Metab., 2000, 279, E395-E402.
Buts, J.P.; De Keyser, N.; Kolanowski, J.; Sokal, E.; Van Hoof, F. Maturation of villus and crypt cell functions in rat small intestine. Role of dietary polyamines. Dig. Dis. Sci., 1993, 38, 1091-1098.
Fusi, E.; Baldi, A.; Cheli, F.; Rebucci, R.; Ayuso, E.; Sejrsen, K.; Purup, S. Effects of putrescine, cadaverine, spermine, spermidine and β-phenylethylamine on cultured bovine mammary epithelial cells. Ital. J. Anim. Sci., 2008, 7(2), 131-140.
Gerner, E.W. Impact of dietary amino acids and polyamines on intestinal carcinogenesis and chemoprevention in mouse models. Biochem. Soc. Trans., 2007, 35, 322-325.
Cao, W.; Liu, G.M.; Fang, T.T.; Wu, X.J.; Jia, G.; Zhao, H.; Chen, X.L.; Wu, C.M.; Wang, J.; Cai, J.Y. Effects of spermine on the morphology, digestive enzyme activities, and antioxidant status of jejunum in suckling rats. RSC Adv, 2015, 5, 76607-76614.
Barszcz, M.; Skomial, J. The development of the small intestine of piglets - chosen aspects. J. Anim. Feed Sci., 2011, 20, 3-15.
Wang, J.Y. Polyamines and mRNA stability in regulation of intestinal mucosal growth. Amino Acids, 2007, 33, 241-252.
de Silanes, I.L.; Zhan, M.; Lal, A.; Yang, X.L.; Gorospe, M. Identification of a target RNA motif for RNA-binding protein HuR. Proc. Natl. Acad. Sci. USA, 2004, 101, 2987-2992.
Zhang, X.; Zou, T.T.; Rao, J.N.; Liu, L.; Xiao, L.; Wang, P.Y.; Cui, Y.H.; Gorospe, M.; Wang, J.Y. Stabilization of XIAP mRNA through the RNA binding protein HuR regulated by cellular polyamines. Nucleic Acids Res., 2009, 37, 7623-7637.
Ray, R.M.; Zimmerman, B.J.; McCormack, S.A.; Patel, T.B.; Johnson, L.R. Polyamine depletion arrests cell cycle and induces inhibitors p21(Waf1/Cip1), p27(Kip1), and p53 in IEC-6 cells. Am. J. Physiol., 1999, 276, C684-C691.
Song, P.; Zhang, R.; Wang, X.; He, P.; Tan, L.; Ma, X. Dietary grape-seed procyanidins decreased postweaning diarrhea by modulating intestinal permeability and suppressing oxidative stress in rats. J. Agric. Food Chem., 2011, 59, 6227-6232.
Fan, P.; Tan, Y.; Jin, K.; Lin, C.; Xia, S.; Han, B.; Zhang, F.; Wu, L.; Ma, X. Supplemental lipoic acid relieves post-weaning diarrhoea by decreasing intestinal permeability in rats. J. Anim. Physiol. Anim. Nutr. (Berl.), 2017, 101, 136-146.
Zhao, J.; Liu, P.; Wu, Y.; Guo, P.; Liu, L.; Ma, N.; Levesque, C.; Chen, Y.; Zhao, J.; Zhang, J.; Ma, X. Dietary fiber increases butyrate-producing bacteria and improves the growth performance of weaned piglets. J. Agric. Food Chem., 2018, 66, 7995-8004.
Zhou, Y.; Ni, X.; Wen, B.; Duan, L.; Sun, H.; Yang, M.; Zou, F.; Lin, Y.; Liu, Q.; Zeng, Y.; Fu, X.; Pan, K.; Jing, B.; Wang, P.; Zeng, D. Appropriate dose of Lactobacillus buchneri supplement improves intestinal microbiota and prevents diarrhoea in weaning Rex rabbits. Benef. Microbes, 2018, 9, 401-416.
Mogensen, N.; Saermark, T.; Vilhardt, H. Endocytosis of the vasopressin receptor by anterior pituitary cells is increased by corticotropin-releasing factor (CRF). Regul. Pept., 1988, 20, 223-231.

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