Research Progress on Mechanism of Micronutrient Zinc Promoting Development and Regeneration of Intestinal Epithelium

  • ZHANG Dexiang ,
  • ZHU Qiujie ,
  • LIU Zhenhua ,
  • WANG Xiuqi
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  • Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou 510642, China

Received date: 2020-04-07

  Online published: 2020-11-16

Abstract

Zinc, an essential trace element, is an important component of many enzymes, which, as a cofactor, participates in protein activation, folding and functional regulation. Zinc is mainly absorbed in the small intestine, and zinc homeostasis is regulated by zinc transporters, osmotic channels and metallothionein. The abnormality of zinc homeostasis leads to the dysfunction of intestinal structure and barrier, and hinders the growth and development of the body. In addition, zinc can recognize cellular signals, increase intestinal stem cell activity by regulating the Wnt/β-catenin and mammalian target of rapamycin complex 1 (mTORC1) signaling pathways, and promote intestinal epithelial development and repair after injury. This paper reviewed the transport system of zinc in the intestine and its regulatory mechanism for intestinal renewal and regeneration, in order to provide new ideas for the development and application of zinc preparations.

Cite this article

ZHANG Dexiang , ZHU Qiujie , LIU Zhenhua , WANG Xiuqi . Research Progress on Mechanism of Micronutrient Zinc Promoting Development and Regeneration of Intestinal Epithelium[J]. Chinese Journal of Animal Nutrition, 2020 , 32(11) : 5038 -5045 . DOI: 10.3969/j.issn.1006-267x.2020.11.008

References

[1] MCCALL K A,HUANG C C,FIERKE C A.Function and mechanism of zinc metalloenzymes[J].The Journal of Nutrition,2000,130(5):1437S-1446S.
[2] 陈良妹,董晓明,杨帆,等.锌缺乏症对慢性肾脏病发展的影响及其作用机制的研究进展[J].吉林大学学报(医学版),2018,44(1):195-199.
[3] TANEJA S K,JAIN M,MANDAL R,et al.Excessive zinc in diet induces leptin resistance in Wistar rat through increased uptake of nutrients at intestinal level[J].Journal of Trace Elements in Medicine and Biology,2012,26(4):267-272.  
[4] 罗治彬,吴嘉惠,徐采朴.过量锌对大鼠小肠粘膜SIgA免疫的影响[J].细胞与分子免疫学杂志,1998(4):295-296.
[5] 于昱,罗绪刚,吕林,等.动物小肠锌吸收特点及其机制的研究进展[J].肠外与肠内营养,2006,13(3):179-183,187.
[6] 高建伟,王林枫,杨改青,等.锌的消化吸收机制研究进展[J].安徽农业科学,2010,38(1):33-34,67.
[7] KREBS N F,HAMBIDGE K M,WESTCOTT J E,et al.Exchangeable zinc pool size in infants is related to key variables of zinc homeostasis[J].The Journal of Nutrition,2003,133(5):1498S-1501S.
[8] JOU M Y,PHILIPPS A F,KELLEHER S L,et al.Effects of zinc exposure on zinc transporter expression in human intestinal cells of varying maturity[J].Journal of Pediatric Gastroenterology and Nutrition,2010,50(6):587-595.  
[9] GAITHER L A,EIDE D J.Functional expression of the human hZIP2 zinc transporter[J].Journal of Biological Chemistry,2000,275(8):5560-5564.  
[10] HUANG L P,GITSCHIER J.A novel gene involved in zinc transport is deficient in the lethal milk mouse[J].Nature Genetics,1997,17(3):292-297.  
[11] KAMBE T,YAMAGUCHI-IWAI Y,SASAKI R,et al.Overview of mammalian zinc transporters[J].Cellular and Molecular Life Sciences,2004,61(1):49-68.  
[12] COUSINS R J,LIUZZI J P,LICHTEN L A.Mammalian zinc transport,trafficking,and signals[J].Journal of Biological Chemistry,2006,281(34):24085-24089.  
[13] 于昱,王福俤.锌转运蛋白家族SLC39A/ZIP和SLC30A/ZnT的研究进展[J].中国细胞生物学学报,2010,32(2):176-188.
[14] KELLEHER S L,LOPEZ V,LÖNNERDAL B,et al.Zip3(Slc39a3) functions in zinc reuptake from the alveolar lumen in lactating mammary gland[J].American Journal of Physiology:Regulatory Integrative and Comparative Physiology,2009,297(1):R194-R201.
[15] LICHTEN L A,COUSINS R J.Mammalian zinc transporters:nutritional and physiologic regulation[J].Annual Review of Nutrition,2009,29:153-176.
[16] GEISER J,VENKEN K J T,DE LISLE R C,et al.A mouse model of acrodermatitis enteropathica:loss of intestine zinc transporter ZIP4(Slc39a4) disrupts the stem cell niche and intestine integrity[J].PLoS Genetics,2012,8(6):e1002766.
[17] DUFNER-BEATTIE J,KUO Y M,GITSCHIER J,et al.The adaptive response to dietary zinc in mice involves the differential cellular localization and zinc regulation of the zinc transporters ZIP4 and ZIP5[J].Journal of Biological Chemistry,2004,279(47):49082-49090.  
[18] 乔珏,夏海滨.锌离子转运蛋白LIV-1的研究进展[J].现代肿瘤医学,2014,22(6):1454-1458.
[19] OLLIG J,KLOUBERT V,TAYLOR K M,et al.B cell activation and proliferation increase intracellular zinc levels[J].The Journal of Nutritional Biochemistry,2019,64:72-79.
[20] PALMITER R D.Protection against zinc toxicity by metallothionein and zinc transporter[J].Proceedings of the National Academy of Sciences of the United States of America,2004,101(14):4918-4923.  
[21] YU Y Y,KIRSCHKE C P,HUANG L P.Immunohistochemical analysis of ZnT1,4,5,6,and 7 in the mouse gastrointestinal tract[J].Journal of Histochemistry & Cytochemistry,2007,55(3):223-234.  
[22] YAMAJI S,TENNANT J,TANDY S,et al.Zinc regulates the function and expression of the iron transporters DMT1 and IREG1 in human intestinal Caco-2 cells[J].FEBS Letters,2001,507(2):137-141.  
[23] YASUNO T,OKAMOTO H,NAGAI M,et al.In vitro study on the transport of zinc across intestinal epithelial cells using Caco-2 monolayers and isolated rat intestinal membranes[J].Biological and Pharmaceutical Bulletin,2012,35(4):588-593.  
[24] TAYLOR K M,NICHOLSON R I.The LZT proteins;the LIV-1 subfamily of zinc transporters[J].Biochimica et Biophysica Acta:Biomembranes,2003,1611(1/2):16-30.
[25] SHEN H,QIN H H,GUO J S.Cooperation of metallothionein and zinc transporters for regulating zinc homeostasis in human intestinal Caco-2 cells[J].Nutrition Research,2008,28(6):406-413.  
[26] HOLLAND T C,KILLILEA D W,SHENVI S V,et al.Acute changes in cellular zinc alters zinc uptake rates prior to zinc transporter gene expression in Jurkat cells[J].BioMetals,2015,28(6):987-996.  
[27] TAKO E,FERKET P R,UNI Z.Changes in chicken intestinal zinc exporter mRNA expression and small intestinal functionality following intra-amniotic zinc-methionine administration[J].The Journal of Nutritional Biochemistry,2005,16(6):339-346.  
[28] LIU H W,LIU D S,ZHENG L X.Study on Zn relative concentration and chemical state in broilers duodenum by micro-X-ray fluorescence and micro-X-ray absorption fine structure[J].Livestock Science,2014,161:101-108.
[29] ZHOU J Y,LIN H L,WANG Z,et al.Zinc L-Aspartate enhances intestinal stem cell activity to protect the integrity of the intestinal mucosa against deoxynivalenol through activation of the Wnt/β-catenin signaling pathway[J].Environmental Pollution,2020,262:114290.
[30] YUE M,FANG S L,ZHUO Z,et al.Zinc glycine chelate absorption characteristics in sprague dawley rat[J].Journal of Animal Physiology and Animal Nutrition,2015,99(3):457-464.  
[31] HUANG D P,ZHUO Z,FANG S L,et al.Different zinc sources have diverse impacts on gene expression of zinc absorption related transporters in intestinal porcine epithelial cells[J].Biological Trace Element Research,2016,173(2):325-332.  
[32] YEUNG T M,CHIA L A,KOSINSKI C M,et al.Regulation of self-renewal and differentiation by the intestinal stem cell niche[J].Cellular and Molecular Life Sciences,2011,68(15):2513-2523.  
[33] AMCHESLAVSKY A,NIE Y C,LI Q,et al.Gene expression profiling identifies the zinc-finger protein Charlatan as a regulator of intestinal stem cells in Drosophila[J].Development,2014,141(13):2621-2632.  
[34] OHASHI W,KIMURA S,IWANAGA T,et al.Zinc transporter SLC39A7/ZIP7 promotes intestinal epithelial self-renewal by resolving ER stress[J].PLoS Genetics,2016,12(10):e1006349.
[35] BLANCHARD R K,COUSINS R J.Differential display of intestinal mRNAs regulated by dietary zinc[J].Proceedings of the National Academy of Sciences of the United States of America,1996,93(14):6863-6868.  
[36] DUFF M,ETTARH R R.Crypt cell production rate in the small intestine of the zinc-supplemented mouse[J].Cells Tissues Organs,2002,172(1):21-28.  
[37] 郑立鑫,刘华伟,吴鹏华,等.不同锌源对肉仔鸡肠道形态及金属硫蛋白表达的影响[J].中国饲料,2013(20):7-10.
[38] ZHANG B K,GUO Y M.Supplemental zinc reduced intestinal permeability by enhancing occludin and zonula occludens protein-1(ZO-1) expression in weaning piglets[J].British Journal of Nutrition,2009,102(5):687-693.  
[39] SHAO Y X,WOLF P G,GUO S S,et al.Zinc enhances intestinal epithelial barrier function through the PI3K/AKT/mTOR signaling pathway in Caco-2 cells[J].The Journal of Nutritional Biochemistry,2017,43:18-26.
[40] 金美林,岳小婧,莫才红,等.日粮添加黄芪和锌对肉鸡生产性能、肠道微生物及抗氧化能力的影响[J].中兽医医药杂志,2017,36(4):55-58.
[41] CARIO E,JUNG S,D'HEUREUSE J H,et al.Effects of exogenous zinc supplementation on intestinal epithelial repair in vitro[J].European Journal of Clinical Investigation,2000,30(5):419-428.  
[42] HAN X Y,MA Y F,LV M Y,et al.Chitosan-zinc chelate improves intestinal structure and mucosal function and decreases apoptosis in ileal mucosal epithelial cells in weaned pigs[J].British Journal of Nutrition,2014,111(8):1405-1411.  
[43] HOLODOVA M,COBANOVA K,SEFCIKOVA Z,et al.Dietary zinc and fibre source can influence the mineral and antioxidant status of piglets[J].Animals,2019,9(8):497.
[44] TRAN C D,HAWKES J,GRAHAM R D,et al.Zinc-fortified oral rehydration solution improved intestinal permeability and small intestinal mucosal recovery[J].Clinical Pediatrics,2015,54(7):676-682.  
[45] MAHMOOD A,FITZGERALD A J,MARCHBANK T,et al.Zinc carnosine,a health food supplement that stabilises small bowel integrity and stimulates gut repair processes[J].Gut,2007,56(2):168-175.  
[46] TRAN C D,HOWARTH G S,COYLE P,et al.Dietary supplementation with zinc and a growth factor extract derived from bovine cheese whey improves methotrexate-damaged rat intestine[J].The American Journal of Clinical Nutrition,2003,77(5):1296-1303.  
[47] ZHANG B K,GUO Y M.Beneficial effects of tetrabasic zinc chloride for weanling piglets and the bioavailability of zinc in tetrabasic form relative to ZnO[J].Animal Feed Science and Technology,2007,135(1/2):75-85.
[48] POULSEN H D.Zinc oxide for weanling piglets[J].Acta Agriculturae Scandinavica,SectionA:Animal Sciences,1995,45(3):159-167.  
[49] CARLSON D,POULSEN H D,SEHESTED J.Influence of weaning and effect of post weaning dietary zinc and copper on electrophysiological response to glucose,theophylline and 5-HT in piglet small intestinal mucosa[J].Comparative Biochemistry and Physiology Part A:Molecular & Integrative Physiology,2004,137(4):757-765.  
[50] CARLSON D,SEHESTED J,FENG Z,et al.Serosal zinc attenuate serotonin and vasoactive intestinal peptide induced secretion in piglet small intestinal epithelium in vitro[J].Comparative Biochemistry and Physiology Part A:Molecular & Integrative Physiology,2008,149(1):51-58.  
[51] OU D Y,LI D F,CAO Y H,et al.Dietary supplementation with zinc oxide decreases expression of the stem cell factor in the small intestine of weanling pigs[J].The Journal of Nutritional Biochemistry,2007,18(12):820-826.  
[52] 张崇远.葡萄糖酸锌治疗儿童腹泻作用机制研究进展[J].中国处方药,2017,15(10):18-19.
[53] ZHU M,WANG X Q.Regulation of mTORC1 by small GTPases in response to nutrients[J].The Journal of Nutrition,2020,150(5):1004-1011,doi:10.1093/jn/nxz301.
[54] 朱秋杰,周加义,梁少杰,等.Wnt/β-连环蛋白信号驱动小肠上皮更新和再生机制的研究进展[J].动物营养学报,2019,31(11):4995-5002.
[55] ZHOU J Y,WANG Z,ZHANG S W,et al.Methionine and its hydroxyl analogues improve stem cell activity to eliminate deoxynivalenol-induced intestinal injury by reactivating Wnt/β-catenin signaling[J].Journal of Agricultural and Food Chemistry,2019,67(41):11464-11473.  
[56] LI X G,ZHU M,CHEN M X,et al.Acute exposure to deoxynivalenol inhibits porcine enteroid activity via suppression of the Wnt/β-catenin pathway[J].Toxicology Letters,2019,305:19-31.
[57] ZHOU J Y,ZHANG S W,LIN H L,et al.Hydrolyzed wheat gluten alleviates deoxynivalenol-induced intestinal injury by promoting intestinal stem cell proliferation and differentiation via upregulation of Wnt/β-catenin signaling in mice[J].Food and Chemical Toxicology,2019,131:110579.
[58] ZHU M,QIN Y C,GAO C Q,et al.L-glutamate drives porcine intestinal epithelial renewal by increasing stem cell activity via upregulation of the EGFR-ERK-mTORC1 pathway[J].Food & Function,2020,11(3):2714-2724.  
[59] ZHU M,QIN Y C,GAO C Q,et al.Extracellular glutamate-induced mTORC1 activation via the IR/IRS/PI3K/Akt pathway enhances the expansion of porcine intestinal stem cells[J].Journal of Agricultural and Food Chemistry,2019,67(34):9510-9521.  
[60] ZHOU J Y,HUANG D G,QIN Y C,et al.mTORC1 signaling activation increases intestinal stem cell activity and promotes epithelial cell proliferation[J].Journal of Cellular Physiology,2019,234(10):19028-19038.  
[61] STRUBBERG A M,PANIAGUA D A V,ZHAO T T,et al.The zinc finger transcription factor PLAGL2 enhances stem cell fate and activates expression of ASCL2 in intestinal epithelial cells[J].Stem Cell Reports,2018,11(2):410-424.  
[62] LI X G,WANG Z,CHEN R Q,et al.Lgr5 and Bmi1 increase pig intestinal epithelial cell proliferation by stimulating Wnt/β-catenin signaling[J].International Journal of Molecular Sciences,2018,19(4):1036-1048.  
[63] MACDONALD B T,TAMAI K,HE X.Wnt/β-catenin signaling:components,mechanisms,and diseases[J].Developmental Cell,2009,17(1):9-26.  
[64] NIMMANON T,ZILIOTTO S,MORRIS S,et al.Phosphorylation of zinc channel ZIP7 drives MAPK,PI3K and mTOR growth and proliferation signalling[J].Metallomics,2017,9(5):471-481.  
[65] LYNCH C J,PATSON B J,GOODMAN S A,et al.Zinc stimulates the activity of the insulin- and nutrient-regulated protein kinase mTOR[J].American Journal of Physiology:Endocrinology and Metabolism,2001,281(1):E25-E34.
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