{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:01:50Z","timestamp":1790182910635,"version":"4.1.0"},"reference-count":47,"publisher":"American Physiological Society","issue":"2","funder":[{"name":"Dept. of Science & Technology, Govt. of India"},{"DOI":"10.13039\/501100001501","name":"University Grants Commission (University Grants Commission India)","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001501","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research (ICMR)","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dept. of Biotechnology, Govt. of India","award":["BT\/ PR6462\/FNS\/20\/669\/2012"],"award-info":[{"award-number":["BT\/ PR6462\/FNS\/20\/669\/2012"]}]},{"name":"NIH\/NIDDK","award":["RO1DK018777"],"award-info":[{"award-number":["RO1DK018777"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2019,2,1]]},"abstract":"<jats:p>\n                    Whether zinc (Zn\n                    <jats:sup>2+<\/jats:sup>\n                    ) regulates barrier functions by modulating tight-junction (TJ) proteins when pathogens such as Shigella alter epithelial permeability is still unresolved. We investigated the potential benefits of Zn\n                    <jats:sup>2+<\/jats:sup>\n                    in restoring impaired barrier function in vivo in Shigella-infected mouse tissue and in vitro in T84 cell monolayers. Basolateral Shigella infection triggered a time-dependent decrease in transepithelial resistance followed by an increase in paracellular permeability of FITC-labeled dextran and altered ion selectivity. This led to ion and water loss into the intestinal lumen. Immunofluorescence studies revealed redistribution of claudin-2 and -4 to an intracellular location and accumulation of these proteins in the cytoplasm following infection. Zn\n                    <jats:sup>2+<\/jats:sup>\n                    ameliorated this perturbed barrier by redistribution of claudin-2 and -4 back to the plasma membrane and by modulating the phosphorylation state of TJ proteins t hough extracellular signal-regulated kinase (ERK)1\/2 dependency. Zn\n                    <jats:sup>2+<\/jats:sup>\n                    prevents elevation of IL-6 and IL-8. Mice challenged with Shigella showed that oral Zn\n                    <jats:sup>2+<\/jats:sup>\n                    supplementation diminished diverse pathophysiological symptoms of shigellosis. Claudin-2 and -4 were susceptible to Shigella infection, resulting in altered barrier function and increased levels of IL-6 and IL-8. Zn\n                    <jats:sup>2+<\/jats:sup>\n                    supplementation ameliorated this barrier dysfunction, and the inflammatory response involving ERK-mediated change of phosphorylation status for claudin-2 and -4. Thus, Zn\n                    <jats:sup>2+<\/jats:sup>\n                    may have potential therapeutic value in inflammatory diarrhea and shigellosis.\n                  <\/jats:p>\n                  <jats:p>\n                    NEW &amp; NOTEWORTHY Our study addresses whether Zn\n                    <jats:sup>2+<\/jats:sup>\n                    could be an alternative strategy to reduce Shigella-induced inflammatory response and epithelial barrier dysfunction. We have defined a mechanism in terms of intracellular signaling pathways and tight-junction protein expression by Zn\n                    <jats:sup>2+<\/jats:sup>\n                    . Claudin-2 and -4 are susceptible to Shigella infection, whereas in the presence of Zn\n                    <jats:sup>2+<\/jats:sup>\n                    they are resistant to infection-related barrier dysfunction involving ERK-mediated change of phosphorylation status of claudins.\n                  <\/jats:p>","DOI":"10.1152\/ajpgi.00092.2018","type":"journal-article","created":{"date-parts":[[2018,11,8]],"date-time":"2018-11-08T07:27:54Z","timestamp":1541662074000},"page":"G229-G246","source":"Crossref","is-referenced-by-count":33,"title":["Zinc ameliorates intestinal barrier dysfunctions in shigellosis by reinstating claudin-2 and -4 on the membranes"],"prefix":"10.1152","volume":"316","author":[{"given":"Paramita","family":"Sarkar","sequence":"first","affiliation":[{"name":"Molecular Pathophysiology Division, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, 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