The DOI matches its Crossref record; 37 of the 38 references it cites were found in a registry or an index.
Cellular zinc is required for intestinal epithelial barrier maintenance via the regulation of claudin-3 and occludin expression
Open accessAbstract
Intracellular zinc is required for a variety of cell functions, but its precise roles in the maintenance of the intestinal tight junction (TJ) barrier remain unclear. The present study investigated the essential roles of intracellular zinc in the preservation of intestinal TJ integrity and the underlying molecular mechanisms. Depletion of intracellular zinc in both intestinal Caco-2 cells and mouse colons through the application of a cell-permeable zinc chelator N, N, N′, N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) induced a disruption of the TJ barrier, as indicated by increased FITC-labeled dextran flux and decreased transepithelial electrical resistance. The TPEN-induced TJ disruption is associated with downregulation of two TJ proteins, occludin and claudin-3. Biotinylation of cell surface proteins revealed that the zinc depletion induced the proteolysis of occludin but not claudin-3. Occludin proteolysis was sensitive to the inhibition of calpain activity, and increased calpain activity was observed in the zinc-depleted cells. Although quantitative PCR analysis and promoter reporter assay have demonstrated that the zinc depletion-induced claudin-3 downregulation occurred at transcriptional levels, a site-directed mutation in the egr1 binding site in the claudin-3 promoter sequence induced loss of both the basal promoter activity and the TPEN-induced decreases. Reduced egr1 expression by a specific siRNA also inhibited claudin-3 expression and transepithelial electrical resistance maintenance in cells. This study shows that intracellular zinc has an essential role in the maintenance of the intestinal epithelial TJ barrier through regulation of occludin proteolysis and claudin-3 transcription.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Zinc strengthens tight junctions through regulation of occludin proteolysis and claudin-3 transcription [290], increases mucus production, and reduces gastric acid secretion [184,291,292], while also promoting wound healing [293].”
From Nutritional Approaches to Enhance GLP-1 Analogue Therapy in Obesity: A Narrative Review (2025) · cites this paper as [293]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961
Intestinal mucosal barrier function in health and disease
Turner, J. R. (2009) · Nature reviews. Immunology · doi:10.1038/nri2653 · Cited by 3,952
Occludin: a novel integral membrane protein localizing at tight junctions.
Furuse, M., Hirase, T., Itoh, M., Nagafuchi, A., Yonemura, S., Tsukita, S., & Tsukita, S. (1993) · The Journal of cell biology · doi:10.1083/jcb.123.6.1777 · Cited by 2,580
Furuse, M., Fujita, K., Hiiragi, T., Fujimoto, K., & Tsukita, S. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.141.7.1539 · Cited by 2,100
Regulation of intestinal epithelial permeability by tight junctions
Suzuki, T. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1070-x · Cited by 1,437
Self-citationZeißig, S., Bürgel, N., Günzel, D., Richter, J. F., Mankertz, J., Wahnschaffe, U., Kroesen, A. J., Zeitz, M., Fromm, M., & Schulzke, J. (2006) · Gut · doi:10.1136/gut.2006.094375 · Cited by 1,218
Complex Phenotype of Mice Lacking Occludin, a Component of Tight Junction Strands
Saitou, M., Furuse, M., Sasaki, H., Schulzke, J.-D., Fromm, M., Takano, H., Noda, T., & Tsukita, S. (2000) · Molecular Biology of the Cell · doi:10.1091/mbc.11.12.4131 · Cited by 1,195
Itoh, M., Furuse, M., Morita, K., Kubota, K., Saitou, M., & Tsukita, S. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.6.1351 · Cited by 1,151
Zinc and its importance for human health: An integrative review.
Roohani, N., Hurrell, R. F., Kelishadi, R., & Schulin, R. (2013) · Europe PMC (PubMed Central) · Cited by 993
Wang, F., Graham, W. V., Wang, Y., Witkowski, E. D., Schwarz, B. T., & Turner, J. R. (2005) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)62264-x · Cited by 692
Research works printed but not linked: 3
- Prasad AS, 1963, J Lab Clin Med, 61, 537
- Roohani N, 2013, J Res Med Sci, 18, 144
- 10.1097/00054725-200105000-00003 · DOI
Cited by
Sorted by citations
Regulation of the intestinal barrier by nutrients: The role of tight junctions
Suzuki, T. (2020) · Animal Science Journal · doi:10.1111/asj.13357 · Cited by 796
Self-citationMaywald, M., Wessels, I., & Rink, L. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18102222 · Cited by 309
Cresci, G., Glueck, B., McMullen, M. R., Xin, W., Allende, D., & Nagy, L. E. (2017) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.13731 · Cited by 146
The Impact of Zinc and Zinc Homeostasis on the Intestinal Mucosal Barrier and Intestinal Diseases
Wan, Y., & Zhang, B. (2022) · Biomolecules · doi:10.3390/biom12070900 · Cited by 128
“[38] also found that the tight junction permeability in Caco2 cells increased in the presence of zinc deficiency, and cell viability was significantly reduced.”
BackgroundNonalcoholic Fatty Liver Disease and the Gut-Liver Axis: Exploring an Undernutrition Perspective
Bauer, K. C., Littlejohn, P. T., Ayala, V., Creus-Cuadros, A., & Finlay, B. B. (2022) · Gastroenterology · doi:10.1053/j.gastro.2022.01.058 · Cited by 127
Liu, M., Yang, J., Zhang, Y., Zhou, Z., Cui, X., Zhang, L., Fung, K.-M. A., Zheng, W., Allard, F. D., Yee, E. U., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0263 · Cited by 106
“Zinc deficiency is known to result in epithelial barrier leak in the pancreas (11) and correlates to reduced levels of the tight junction proteins ZO-1 and claudin-1 through damaging the integrity of the cell connection structure (12).”
BackgroundName, J. J., Souza, A. C. R., Vasconcelos, A. R., Prado, P. S., & Pereira, C. P. M. (2020) · Frontiers in Nutrition · doi:10.3389/fnut.2020.606398 · Cited by 114
Dithmer, S., Blasig, I. E., Fraser, P. A., Qin, Z., & Haseloff, R. F. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115601 · Cited by 101
Barmeyer, C., Fromm, M., & Schulzke, J. (2016) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-016-1914-6 · Cited by 91
Zhang, C., Li, Q., Xing, J., Yang, Y., Zhu, M., Lin, L., Yu, Y., Cai, X., & Wang, X. (2024) · Acta Biomaterialia · doi:10.1016/j.actbio.2024.02.015 · Cited by 90
Metallobiology of Lactobacillaceae in the gut microbiome
Huynh, U., & Zastrow, M. L. (2022) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2022.112023 · Cited by 86
Zinc and Selenium in Inflammatory Bowel Disease: Trace Elements with Key Roles?
Vaghari‐Tabari, M., Jafari-Gharabaghlou, D., Sadeghsoltani, F., Hassanpour, P., Qujeq, D., Rashtchizadeh, N., & Ghorbanihaghjo, A. (2020) · Biological Trace Element Research · doi:10.1007/s12011-020-02444-w · Cited by 71
“of zinc can attenuate the intestinal mucosal barrier [160].”
BackgroundAL-Ayadhi, L. Y., Zayed, N., Bhat, R. S., Moubayed, N., Al-Muammar, M. N., & El-Ansary, A. (2021) · Gut Pathogens · doi:10.1186/s13099-021-00448-y · Cited by 78
“Zinc maintains the mucosal barriers by enhancing the expression of occludin and ZO-1 proteins, resulting in the tightening of junctions [107, 108].”
BackgroundContribution of Zinc and Zinc Transporters in the Pathogenesis of Inflammatory Bowel Diseases
Ohashi, W., & Fukada, T. (2019) · Journal of Immunology Research · doi:10.1155/2019/8396878 · Cited by 74
“Depletion of zinc induces occludin-3 proteolysis and decreased claudin-3 transcription [94].”
Implications of AMPK in the Formation of Epithelial Tight Junctions
Rowart, P., Wu, J., Caplan, M. J., & Jouret, F. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19072040 · Cited by 74
Velasco, E., Wang, S., Sanet, M., Fernández‐Vázquez, J., Jové, D., Glaría, E., Valledor, A. F., O’Halloran, T. V., & Balsalobre, C. (2018) · Scientific Reports · doi:10.1038/s41598-018-24964-1 · Cited by 66
Aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier
Hu, X., Xiao, W., Lei, Y., Green, A., Lee, X., Maradana, M. R., Gao, Y., Xie, X., Wang, R., Chennell, G., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41168-y · Cited by 62
“…presence of 10 µ M EVP4593, zinc and/or FICZ had no stimulatory effect on expression of ZO-1 and OCLN ,indicatingthatzincandFICZincreaseexpressionofmRNAforTJ proteins by alleviating transcriptional inhibition by NF-κ ß. TJproteinsare degradedby calpain proteases,whichareinhibited by zinc 35,36 .”
Callaghan, P. J., Ferrick, B. J., Rybakovsky, E., Thomas, S., & Mullin, J. M. (2020) · Bioscience Reports · doi:10.1042/bsr20201532 · Cited by 56
“such leak occurs with only moderate changes in only a few TJ protein expression levels (Figure 6); and 7) the commonly used barrier-enhancing micronutrients, zinc and quercetin [44-49], are surprisingly unable to improve barrier function across 16HBE cell layers (Figure 7).”
BackgroundMohanty, S., Kamolvit, W., Scheffschick, A., Björklund, A., Tovi, J., Espinosa, A., Brismar, K., Nyström, T., Schröder, J., Östenson, C., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32636-y · Cited by 57
Ammonia impairs tight junction barriers by inducing mitochondrial dysfunction in Caco‐2 cells
Yokoo, K., Yamamoto, Y., & Suzuki, T. (2021) · The FASEB Journal · doi:10.1096/fj.202100758r · Cited by 55
Self-citationAccarie, A., L’Homme, B., Benadjaoud, M. A., Lim, S. K., Guha, C., Benderitter, M., Tamarat, R., & Sémont, A. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-01887-1 · Cited by 51
Roscioli, E., Jersmann, H. P. A., Lester, S. E., Badiei, A., Fon, A., Zalewski, P. D., & Hodge, S. J. (2017) · International Journal of COPD · doi:10.2147/copd.s149589 · Cited by 49
Present and Future Therapeutic Approaches to Barrier Dysfunction
Fortea, M., Albert-Bayo, M., Abril-Gil, M., Mall, J. G., Serra-Ruiz, X., Henao-Paez, A., Expósito, E., González-Castro, A. M., Guagnozzi, D., Lobo, B., et al. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.718093 · Cited by 49
Horst, E. A., Mayorga, E. J., Al‐Qaisi, M., Rodríguez-Jiménez, S., Goetz, B. M., Abeyta, M. A., Gorden, P. J., Kvidera, S. K., & Baumgard, L. H. (2020) · Journal of Dairy Science · doi:10.3168/jds.2020-18860 · Cited by 48
“, 2018), lung (Bao and Knoell, 2006), and intestinal epithelial integrity (SanzFernandez et al., 2014; Miyoshi et al., 2016; Opgenorth et al., 2021).”
BackgroundShao, Y., Lei, Z., Wolf, P. G., Gao, Y. Q., Guo, Y., & Zhang, B. (2017) · Journal of Nutrition · doi:10.3945/jn.116.243238 · Cited by 45
Lerner, A., & Benzvi, C. (2021) · Toxics · doi:10.3390/toxics9100233 · Cited by 42
Sauer, A. K., Malijauskaite, S., Meleady, P., Boeckers, T. M., McGourty, K., & Grabrucker, A. M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-04052-w · Cited by 44
“Under normal Zn conditions, Zn, through ZnR/GPR39, is activating PKCζ and subsequently activating GSK-3β downstream, thereby maintaining the inactivation of SNAIL/SLUG transcription factors and consequently allowing robust E-cadherin expression [37, 65, 66].”
BackgroundAssociation between irritable bowel syndrome and micronutrients: A systematic review
Bek, S., Teo, Y. N., Tan, X., Fan, K. H., & Siah, K. T. H. (2022) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.15891 · Cited by 42
Zinc in Keratinocytes and Langerhans Cells: Relevance to the Epidermal Homeostasis
Ogawa, Y., Kinoshita, M., Shimada, S., & Kawamura, T. (2018) · Journal of Immunology Research · doi:10.1155/2018/5404093 · Cited by 41
“For example, it has been reported that the chelation of intracellular Zn by TPEN (N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine) downregulates occludin and claudin-3, leading to TJ disruption in the intestinal epithelium [62].”
BackgroundZinc treatment is efficient against Escherichia coli α-haemolysin-induced intestinal leakage in mice
Wiegand, S., Zakrzewski, S. S., Eichner, M., Schulz, E., Günzel, D., Pieper, R., Rosenthal, R., Barmeyer, C., Bleich, A., Dobrindt, U., et al. (2017) · Scientific Reports · doi:10.1038/srep45649 · Cited by 36
Foligné, B., George, F., Standaert‐Vitse, A., Garat, A., Poiret, S., Peucelle, V., Ferreira, S., Sobry, H., Muharram, G., Lucau‐Danila, A., et al. (2020) · The FASEB Journal · doi:10.1096/fj.202000562rr · Cited by 33
Mechanistic insights into the protective impact of zinc on sepsis
Souffriau, J., & Libert, C. (2017) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2017.12.002 · Cited by 31
“vitro studies, the underlying mechanism of this barrier failure may be based on decreased expression of tight junction proteins (occludin and claudin-3) [71].”
Oral Mucosa as a Potential Site for Diagnosis and Treatment of Allergic and Autoimmune Diseases
Gómez-Casado, C., Sánchez‐Solares, J., Izquierdo, E., Díaz-Perales, A., Barber, D., & Escribese, M. (2021) · Foods · doi:10.3390/foods10050970 · Cited by 28
Chaen, Y., Yamamoto, Y., & Suzuki, T. (2019) · Nutrition Research · doi:10.1016/j.nutres.2019.01.004 · Cited by 28
Self-citationThe role of human milk nutrients in preventing necrotizing enterocolitis
Sami, A. S., Frazer, L. C., Miller, C. M., Singh, D. K., Clodfelter, L. G., Orgel, K., & Good, M. L. (2023) · Frontiers in Pediatrics · doi:10.3389/fped.2023.1188050 · Cited by 28
“Similarly, Zn depletion led to the downregulation of occludin and claudin-3 in another study using intestinal Caco-2 cells and ex vivo mouse colons (104).”
BackgroundRole of Zinc in Shaping the Gut Microbiome; Proposed Mechanisms and Evidence from the Literature
Usama, U., Khan, M. J., Fatima, S., & Fatima, S. (2018) · Journal of Gastrointestinal & Digestive System · doi:10.4172/2161-069x.1000548 · Cited by 27
“Zinc also regulates intestinal permeability through occludin proteolysis and occludin transcription and thus protects intestines from the invading molecular ions and pathogens [31].”
BackgroundSantos, H. O. (2021) · Nutrition Reviews · doi:10.1093/nutrit/nuab054 · Cited by 25
Shimizu, Y., & Suzuki, T. (2019) · Nutrition Research · doi:10.1016/j.nutres.2019.07.003 · Cited by 25
Self-citationZinc in sickle cell disease: A narrative review
Miranda, C. T. D. O. F., Vermeulen-Serpa, K. M., Pedro, A. C. C., Brandão‐Neto, J., Vale, S. H. D. L., & Figueiredo, M. S. (2022) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2022.126980 · Cited by 24
Zinc Deficiency and Zinc Supplementation in Allergic Diseases
Maywald, M., & Rink, L. (2024) · Biomolecules · doi:10.3390/biom14070863 · Cited by 23
“The repair and regeneration of the intestinal mucosa can be triggered by exogenous zinc supplementation, leading to restored integrity of the intestinal mucosal barrier morphology and function [153].”
BackgroundLacerda, J. D. H. L. F., Lagos, A. C., Carolino, E., Silva-Herdade, A. S., Silva, M., & Guerreiro, C. S. (2021) · Nutrients · doi:10.3390/nu13020642 · Cited by 27
“- Zinc: it seems to present a crucial role in the intestinal barrier integrity through keeping the expression of occludin and claudin-3 and suppressing the proteolysis of occludin [12].”
Backgroundde Rooij, W. E., Vlieg‐Boerstra, B., Warners, M. J., van Ampting, M. T. J., van Esch, B. C. A. M., Eussen, S. R. B. M., & Bredenoord, A. J. (2021) · Neurogastroenterology & Motility · doi:10.1111/nmo.14291 · Cited by 22
Immunomodulatory Effects of Vitamin D and Zinc on Viral Infection
Rizwan, M., Cheng, K., Gang, Y., Hou, Y., & Wang, C. (2024) · Biological Trace Element Research · doi:10.1007/s12011-024-04139-y · Cited by 25
“…mice colon due to a marked reduction in protein concentrations of occludin and claudin-3, two proteins that are essential for tight junctions, and concentration of 100 M effective in re-establishing homeostasis over the barrier, resulting in a reduction of the tight junction’s permeability [184].”
Jimenez, F. R., Ruggiero, C. H., McKinley, K. L., Koh, J., Roberts, J. F., Triplett, E. W., & Cousins, R. J. (2022) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00244.2022 · Cited by 21
Improvement of Human-Oral-Epithelial-Barrier Function and of Tight Junctions by Micronutrients
Rybakovsky, E., Valenzano, M. C., Deis, R., DiGuilio, K. M., Thomas, S., & Mullin, J. M. (2017) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.7b04203 · Cited by 20
He, Y., Yuan, X., Zuo, H., Li, X., Sun, Y., & Feng, A. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.116697 · Cited by 20
Marzano, M., Fosso, B., Colliva, C., Notario, E., Passeri, D., Intranuovo, M., Gioiello, A., Adorini, L., Pesole, G., Pellicciari, R., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113380 · Cited by 21
Adaption of body zinc pools in weaned piglets challenged with subclinical zinc deficiency
Brügger, D., & Windisch, W. M. (2019) · British Journal Of Nutrition · doi:10.1017/s0007114519000187 · Cited by 15
Hamam, E. T., Awadalla, A., Shokeir, A. A., & Aboul-Naga, A. M. (2022) · Toxicology · doi:10.1016/j.tox.2022.153102 · Cited by 16
Yokoyama, M., Narita, T., Sakurai, H., Katsumata-Kato, O., Sugiya, H., & Fujita‐Yoshigaki, J. (2017) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2017.05.007 · Cited by 15
Hu, Y., Yang, K., Zhang, W., Xue, M., Li, T., Wang, S., Cui, X., Zhang, L., Hu, Y., & Luo, X. (2024) · Animals · doi:10.3390/ani14060979 · Cited by 14
“Cell proliferation plays an important role in maintaining intestinal integrity and barrier function [7].”
BackgroundLockwood, T. D. (2019) · BioMetals · doi:10.1007/s10534-019-00197-1 · Cited by 13
“Calpain is inhibited by Zn21 and activated by Zn21 deficiency (Nakajima et al. 2014; Miyoshi et al. 2016).”
BackgroundMeineri, G., Martello, E., Radice, E., Bruni, N., Saettone, V., Atuahene, D., Armandi, A., Testa, G., & Ribaldone, D. G. (2022) · Animals · doi:10.3390/ani12070812 · Cited by 14
Ma, F., Wo, Y., Shan, Q., Wei, J., Zhao, S., & Sun, P. (2020) · Animal Feed Science and Technology · doi:10.1016/j.anifeedsci.2020.114686 · Cited by 14
Pardo, Z., Seiquer, I., Lachica, M., Nieto, R., Lara, L., & Fernández-Fígares, I. (2022) · Journal of Thermal Biology · doi:10.1016/j.jtherbio.2022.103230 · Cited by 13
Zinc and Inflammatory Bowel Disease: From Clinical Study to Animal Experiment
Peng, X., Yang, Y., Zhong, R., Yang, Y., Fang, Y., Liang, N., & Yuan, S. (2024) · Biological Trace Element Research · doi:10.1007/s12011-024-04193-6 · Cited by 13
“The mechanisms of high colonic permeability are related to the reduced expression of tight junction proteins, including occludin and claudin-3 [100].”
Efficacy of zinc supplementation in the management of acute diarrhoea: a randomised controlled trial
Rerksuppaphol, L., & Rerksuppaphol, S. (2019) · Paediatrics and International Child Health · doi:10.1080/20469047.2019.1673548 · Cited by 12
Brain region- and metal-specific effects of embedded metals in a shrapnel wound model in the rat
Hoffman, J. F., Vergara, V. B., & Kalinich, J. F. (2021) · NeuroToxicology · doi:10.1016/j.neuro.2021.01.001 · Cited by 12
Mitchell, S., & Aydemir, T. B. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1649658 · Cited by 15
Medida, R. L., Sharma, A. K., Guo, Y., Johnston, L. J., Urriola, P. E., Gomez, A. M., & Saqui–Salces, M. (2022) · Journal of Nutritional Science · doi:10.1017/jns.2022.105 · Cited by 11
“Zn restriction that affect overall health((13)) include increased DNA damage((14)), oxidative stress((15)), damage to epithelial barrier((16)) and impaired activity of immune cells((4,17)).”
BackgroundMayangsari, Y., Sugimachi, N., Xu, W., Mano, C., Tanaka, Y., Ueda, O., Sakuta, T., Suzuki, Y., Yamamoto, Y., & Suzuki, T. (2021) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.1c04295 · Cited by 10
Self-citationЦинк (Zn) – значение для организма и здоровья + 30 лучших источников
Наталья, Т., & Татьяна, Е. (2022) · Журнал здорового питания и диетологии · doi:10.59316/.vi19.152 · Cited by 25
Wu, X., Cao, Y., Liu, Y., & Zheng, J. (2024) · Nutrients · doi:10.3390/nu16183192 · Cited by 11
Bando, S. Y., Iamashita, P., Guth, B. E. C., dos Santos, L. F., Fujita, A., Abe, C. M., Ferreira, L., & Moreira‐Filho, C. A. (2017) · PLoS ONE · doi:10.1371/journal.pone.0189613 · Cited by 9
Nutritional Approaches to Enhance GLP-1 Analogue Therapy in Obesity: A Narrative Review
Dias, D. D., Vasconcelos, A. R., Souza, A. C. R., Menezes, C. D., Silva, I. S. T. E., & Name, J. J. (2025) · Obesities · doi:10.3390/obesities5040088 · Cited by 8
“Zinc strengthens tight junctions through regulation of occludin proteolysis and claudin-3 transcription [290], increases mucus production, and reduces gastric acid secretion [184,291,292], while also promoting wound healing [293].”
Determination of the median lethal dose of zinc gluconate in mice and safety evaluation
Wang, Y.-C., Yang, X., Xiao, J., Wei, S., Su, Y., Chen, X.-Q., Huang, T., & Shan, Q.-W. (2024) · BMC Pharmacology and Toxicology · doi:10.1186/s40360-024-00736-8 · Cited by 8
“Zinc deficiency can damage the intestinal barrier integrity, leading to intestinal leakage and allowing pathogenic bacteria and other antigenic substances in the gut to directly contact intestinal epithelial cells (IEC), resulting in sustained mucosal inflammation [4].”
BackgroundZIP4: a promising early diagnostic and therapeutic targets for pancreatic cancer
Tang, Y. L. (2024) · American Journal of Cancer Research · doi:10.62347/avym3477 · Cited by 9
Zhang, Y., Wu, H., HuiLian, C., & Fu, L. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c10318 · Cited by 8
Kido, T., Yanagisawa, H., & Suka, M. (2025) · Immunology · doi:10.1111/imm.13896 · Cited by 9
Nakagawa, Y., & Yamada, S. (2024) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-024-05153-3 · Cited by 8
“…of pro-inflammatory mediators, eventually promoting low-grade mucosal inflammation and visceral pain in irritable bowel syndrome [17, 44, 46, 47, 53] Lower butyrate levels, with no changes in propionate concentrations, are present in fecal samples from those with constipation, diarrhea, and…”
Jimenez, F. R., Ruggiero, C. H., Riva, A., Yu, F., Stafford, L. S., Cross, T. R., Larkin, J., & Cousins, R. J. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2422321121 · Cited by 7
Jeshvaghani, Z. S., Argmann, C., de Vries, M. H., van Es, J. H., Collen, L. V., Kotlarz, D., Sveen, M., Comella, P., Snapper, S. B., Klein, C., et al. (2025) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izaf296 · Cited by 7
Dietary composition of adult eosinophilic esophagitis patients is related to disease severity
Eussen, S. R. B. M., Wielders, S., de Rooij, W. E., van Ampting, M. T. J., van Esch, B. C. A. M., de Vries, J. H. M., Bredenoord, A. J., & Vlieg‐Boerstra, B. (2024) · Immunity Inflammation and Disease · doi:10.1002/iid3.1206 · Cited by 7
Su, J., He, Z., Yu, Y., Lu, M., Wu, Z., & Zhang, D. (2021) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-021-09927-y · Cited by 7
Sampah, M. E., Moore, H., Ahmad, R., Duess, J. W., Lu, P., Lopez, C. M., Steinway, S. N., Scheese, D. J., Raouf, Z., Tsuboi, K., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-52216-6 · Cited by 6
Kalyan, G., Slusser-Nore, A., Dunlevy, J. R., Bathula, C. S., Shabb, J. B., Muhonen, W. W., Somji, S., Sens, D. A., & Garrett, S. H. (2022) · PLoS ONE · doi:10.1371/journal.pone.0267599 · Cited by 6
“However, studies on tight junctions in intestinal epithelium have shown an essential role for Zn in maintaining tight junctional integrity [83].”
BackgroundXu, Y., Twarog, M., Li, N., Banks, A., Schustak, J., Bao, Y., Huang, Q., & Medley, Q. G. (2022) · PLoS ONE · doi:10.1371/journal.pone.0271656 · Cited by 5
Zinc deficiency is associated with the development of ovarian endometrial cysts.
Onuma, T., Mizutani, T., Fujita, Y., Ohgami, N., Ohnuma, S., Kato, M., & Yoshida, Y. (2023) · PubMed Central · Cited by 5
Lockwood, T. D. (2024) · BioMetals · doi:10.1007/s10534-024-00590-5 · Cited by 5
Lachica, M., Pardo, Z., Lara, L., Nieto, R., & Fernández-Fígares, I. (2024) · Animals · doi:10.3390/ani14142033 · Cited by 4
“Zinc is very important as an enzymatic cofactor and structural element for proteins [8]; it increases total hemoglobin, the red blood cell count and hematocrit via the hormone erythropoietin, enhancing the O 2 carrying capacity [9].”
BackgroundThe Mineral Intake and Microbiota
Knez, M., Ranić, M., Stangoulis, J., & Glibetić, M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819265-8.00032-2 · Cited by 4
Nutraceuticals in digestive therapy
Головинская, О., & Wang, C. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821232-5.00030-6 · Cited by 4
Roles of zinc in the gut-liver axis
Grüngreiff, K., Reinhold, D., & Maret, W. (2026) · Annals of Hepatology · doi:10.1016/j.aohep.2026.102188 · Cited by 3
Peanut thresholds in peanut‐allergic children are related to dietary composition
Luiten, D., Biezeveld, M. H., van Doorn, O., Riady, H., Yang, M., Bergsma, F., van der Plas, A., Brand, H. K., Arends, N., de Bruin, A., et al. (2023) · Immunity Inflammation and Disease · doi:10.1002/iid3.841 · Cited by 3
“Zinc and iron have an essential role in the maintenance of intestinal epithelial tight junction barrier via the regulation of claudin‐3 and occluding expression.(10,11) Vitamin D may have an effect on allergen sensitivity, because of the involvement in the maintenance of the intestinal barrier function and several mec…”
BackgroundWong, G. C., Jung, Y., Lee, K. C., Fourie, C., Handley, K. M., Montgomery, J. M., & Taylor, M. W. (2021) · Research Square · doi:10.21203/rs.3.rs-864668/v1 · Cited by 3
Intake of fiber and micronutrients in patients with IBS
Roth, B., Al-Shareef, D., & Ohlsson, B. (2025) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365521.2025.2535721 · Cited by 2
“Intracellular zinc is essential for many cellular functions and the preservation of the intestinal barrier [58].”
Wong, G. C., Jung, Y., Lee, K., Fourie, C., Handley, K. M., Montgomery, J. M., & Taylor, M. W. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1607045 · Cited by 2
Micronutrients- The crucial dietary elements in Covid-19 pandemic: A review
Kumar, S., Moodithaya, S. S., Adithi, K., & Chatterjee, P. K. (2022) · Biomedicine · doi:10.51248/.v42i5.1967 · Cited by 2
Oras, A., Kallionpää, H., Suomi, T., Koskinen, S., Laiho, A., Elo, L. L., Knip, M., Lahesmaa, R., Aints, A., & Uibo, R. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e13147 · Cited by 1
“However, zinc is required for intestinal epithelial barrier maintenance via the regulation of claudin-3 and occludin expression [44].”
BackgroundPardo, Z., Mateos, I., Saro, C., Gaona, R. C., Argüello, H., Lachica, M., Ranilla, M. J., & Fernández-Fígares, I. (2023) · Animals · doi:10.3390/ani13061102 · Cited by 1
Sugiura, S. H., & Satoh, S. (2025) · Elsevier eBooks · doi:10.1016/b978-0-323-90873-3.00014-2 · Cited by 2
Impact of selected nutritional components and lifestyle on human intestinal barrier function
Andrulewicz, M. (2021) · Medycyna Ogólna i Nauki o Zdrowiu · doi:10.26444/monz/139615 · Cited by 1
“Na poziomie molekularnym niedobór cynku prowadzi do zmniejszenia ekspresji okludyny i klaudyny-3, co powoduje zaburzenia funkcji TJ w komórkach Caco-2 [52].”
BackgroundEffect of Infliximab on Radiation-Induced Submandibular Gland Dysfunction in Rats
Zhang, P., Abudunaibi, M., Zhao, Q., Wu, Y., Aihaiti, G., Wu, S., Qi, J., Shi, L., & Xu, H. M. (2023) · Radiation Research · doi:10.1667/rade-22-00192.1 · Cited by 1
“Claudin-3 is a barrier protein that is mainly distributed in the apical-lateral and basolateral membranes of acinar cells in the SMG. Zinc-chelating agents disrupt the TJs barrier by downregulating claudin-3 and occludin in the human intestinal cell line caco-2 ( 43 , 44 ).”
BackgroundChoi, J. (2019) · Mspace (University of Manitoba) · Cited by 1
Burin, Á. M. (2020) · doi:10.11606/t.11.2020.tde-22012020-110430 · Cited by 1
“, 2011), and, more recently, influence on intestinal integrity and histomorphometry (Miyoshi et al., 2016; Shao et al. 2014).”
InfluentialAryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrierPreprint
Hu, X., Xiao, W., Lei, Y., Green, A., Lee, X., Maradana, M. R., Gao, Y., Xie, X., Wang, R., Chennell, G., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.11.03.515052 · Cited by 1
Shaffer, J. E., Mamedova, L. K., DeFrain, J. M., Pandalaneni, K., Amamcharla, J. K., Takiya, C. S., & Bradford, B. J. (2018) · Biological Trace Element Research · doi:10.1007/s12011-018-1556-y
Asowata, E. O. (2019) · UCL Discovery (University College London)
Moog, B. A., Angeles, A. A., Merca, F. E., & Sangel, P. (2021) · Tropical Animal Health and Production · doi:10.1007/s11250-021-03012-7
Wong, G. C., Jung, Y., Lee, K. C., Fourie, C., Handley, K. M., Montgomery, J. M., & Taylor, M. W. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.09.09.459709
“Zinc supplementation enhances and 510 maintains the intestinal barrier by regulating expression of several tight junction proteins 511 [99].”
Background
Metadata
- Authors
- Miyoshi, Y., Tanabe, S., & Suzuki, T.
- Affiliations
- Hiroshima University (JP)
- Corresponding author
- Suzuki, Takuya
- ORCID
- Suzuki, Takuya
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2016-07-01
- Volume
- 311
- Issue
- 1
- Pages
- G105-G116
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- OpenAlex
- W2345985582
- Cited by
- 115
- References
- 38
- Citations by year
- 2026: 12 · 2025: 9 · 2024: 16 · 2023: 9 · 2022: 18 · 2021: 17 · 2020: 9 · 2019: 9 · 2018: 6 · 2017: 9 · 2016: 1
- FWCI
- 4.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- the Salt Science Research Foundation
- the Skylark Food Science Institute
- the Towa Foundation for Food Science & Research
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Keywords
- intracellular zinc, claudin-3, occludin, calpain, transepithelial electrical resistance, intestinal epithelium, tight junction integrity
- MeSH terms
- Animals, Binding Sites, Chelating Agents, Colon, Epithelial Cells, Humans, Intestinal Mucosa, Male, Mice, Inbred ICR, Permeability, Promoter Regions, Genetic, Transcription, Genetic, Transfection, Zinc, Signal Transduction, Electric Impedance, Caco-2 Cells, Tight Junctions, Zinc Sulfate, RNA Interference, Early Growth Response Protein 1, Proteolysis, Claudin-3, Occludin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
