{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:56:24Z","timestamp":1789952184244,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["H2024307018"],"award-info":[{"award-number":["H2024307018"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n Problem<\/jats:title>\n \n Intrauterine growth restriction (IUGR) is a pregnancy complication characterized by failure of the fetus to reach its genetic growth potential. We established the association\n Klotho<\/jats:italic>\n ,\n fibroblast growth factor 23<\/jats:italic>\n (\n FGF23<\/jats:italic>\n ), and\n vascular endothelial growth factor receptor 2<\/jats:italic>\n (\n VEGFR2<\/jats:italic>\n ) with IUGR for the first time, hoping to provide new insights for its diagnosis and treatment.\n <\/jats:p>\n <\/jats:sec>\n \n Method of Study<\/jats:title>\n \n Sixteen pregnant rats were randomly divided into a low\u2010protein diet group (IUGR group) and a control group. Placental tissues were sampled to detect\n Klotho<\/jats:italic>\n ,\n FGF23<\/jats:italic>\n ,\n VEGFR2<\/jats:italic>\n mRNA, and protein expression in placental tissues of pregnant rats using quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR) and western blot. Bioinformatics methods were also used to predict the signaling pathways involved in\n Klotho<\/jats:italic>\n ,\n FGF23<\/jats:italic>\n , and\n VEGFR2<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The weight and crown\u2010rump length of fetal rats in the IUGR group were significantly lower than those in the control group (\n p\u00a0<\/jats:italic>\n <\u00a00.05). The expression levels of\n Klotho<\/jats:italic>\n ,\n FGF23<\/jats:italic>\n , and\n VEGFR2<\/jats:italic>\n in IUGR group placental tissues were significantly lower than those in the control group (\n p\u00a0<\/jats:italic>\n <\u00a00.05). Meanwhile, based on bioinformatics, it was predicted that\n VEGFR2<\/jats:italic>\n might affect the activation of the PI3K\/AKT signaling pathway by growth hormone (GH)\/insulin\u2010like growth factor\u20101(IGF\u20101) through\n Klotho<\/jats:italic>\n \/\n FGF23<\/jats:italic>\n axis inhibition.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n IUGR caused by a low protein diet reduced birth weight and crown\u2010rump length and low expression of\n Klotho<\/jats:italic>\n ,\n FGF23<\/jats:italic>\n , and\n VEGFR2<\/jats:italic>\n in placental tissues, which may inhibit fetal growth through the\n VEGFR2\u2010Klotho\u2010FGF23\u2010<\/jats:italic>\n GH\u2010IGF\u20101\u2010PI3K\u2010AKT signaling axis.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/aji.70110","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T17:45:55Z","timestamp":1755020755000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Down\u2010Regulation of Klotho\/FGF23 by Low\u2010Expressed VEGFR2 Inhibits the GH\/IGF\u20101\/PI3K\/AKT Signaling Pathway Inducing Intrauterine Growth Restriction in Rats"],"prefix":"10.1111","volume":"94","author":[{"given":"Li","family":"Zhang","sequence":"first","affiliation":[{"name":"Graduate School, Hebei North University Zhangjiakou Hebei China"},{"name":"Department of Pediatrics Hebei General Hospital Shijiazhuang Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlu","family":"Zheng","sequence":"additional","affiliation":[{"name":"Graduate School, Hebei North University Zhangjiakou Hebei 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