{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:43:52Z","timestamp":1790833432402,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2016,12,30]],"date-time":"2016-12-30T00:00:00Z","timestamp":1483056000000},"content-version":"vor","delay-in-days":29,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI116323"],"award-info":[{"award-number":["AI116323"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["G20RR024001"],"award-info":[{"award-number":["G20RR024001"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Cryptosporidium,<\/jats:italic>\n                    a ubiquitous coccidian protozoan parasite that infects the gastrointestinal epithelium and other mucosal surfaces, is an important opportunistic pathogen for immunocompromised individuals and a common cause of diarrhea in young children in the developing countries. One of the pathological hallmarks of intestinal cryptosporidiosis is villous atrophy, which results in a shorter height of intestinal villi. Here, we investigated the effects of\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    infection on intestinal epithelial growth, using an ex\u00a0vivo model of intestinal cryptosporidiosis employing enteroids from mice. We detected infection of enteroids isolated from immunocompetent adult and neonatal mice after ex\u00a0vivo exposure to\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    sporozoites. We observed a significant inhibition of enteroid propagation following infection. Intriguingly, we identified a decreased expression level of intestinal stem cell markers in enteroids following\n                    <jats:italic>C.\u00a0parvum<\/jats:italic>\n                    infection. We further measured the expression levels of several Wnt antagonists or agonists in infected enteroids, as induction of the Wnt\/\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010catenin activation is a key factor for intestinal stem cell function. We detected a markedly increased level of the Dickkopf\u2010related protein 1 and decreased level of the Wnt family member 5a in enteroids after infection. The low density lipoprotein receptor\u2010related protein 5, one of the Wnt co\u2010receptors, is downregulated in the infected enteroids. In addition, increased apoptotic cell death and cell senescence were observed in the infected enteroids. Our results demonstrate a significant inhibitory effect of\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    infection on the ex\u00a0vivo propagation of enteroids from mice, providing additional insights into the impact of\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    infection on intestinal epithelial growth.\n                  <\/jats:p>","DOI":"10.14814\/phy2.13060","type":"journal-article","created":{"date-parts":[[2016,12,30]],"date-time":"2016-12-30T21:05:16Z","timestamp":1483131916000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["<i>Cryptosporidium parvum<\/i>\n                    infection attenuates the ex\u00a0vivo propagation of murine intestinal enteroids"],"prefix":"10.14814","volume":"4","author":[{"given":"Xin\u2010Tian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology Creighton University School of Medicine Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai\u2010Yu","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology Creighton University School of Medicine Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology Creighton University School of Medicine Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiqiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology Creighton University School of Medicine Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng\u2010Yau S.","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology Creighton University School of Medicine Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney E.","family":"Dolata","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology Creighton University School of Medicine Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian\u2010Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology Creighton University School of Medicine Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,12,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3721"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06196"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.11.016"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.247866"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05714.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01131-12"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.01.008"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(14)70772-8"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510280402"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra013170"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702633200"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1248012"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2003.10.001"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000060368"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370214529398"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1921510"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003261"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2006.03.006"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.1.131-139.2003"},{"key":"e_1_2_7_21_1","first-page":"13","article-title":"Laboratory animal models for experimental cryptosporidiosis: a minireview","volume":"54","author":"Kim C. 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