{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T12:32:56Z","timestamp":1768480376282,"version":"3.49.0"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T00:00:00Z","timestamp":1594166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102016R1D1A1A02937331"],"award-info":[{"award-number":["NRF\u20102016R1D1A1A02937331"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Glutathione peroxidase 3 (<jats:italic>Gpx3<\/jats:italic>) protects cells from oxidative stress, and its reduced expression in human prostate cancer has been reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We hypothesized that <jats:italic>Gpx3<\/jats:italic> might play an important role in the development of prostatic intraepithelial neoplasia (PIN), a pre\u2010cancerous state of the prostate, and aimed to highlight the underlying molecular mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>The following double\u2010knockout mice <jats:italic>Nkx3.1<\/jats:italic>\u2212\/\u2212<jats:italic>; Gpx3+<\/jats:italic>\/<jats:italic>+, Nkx3.1<\/jats:italic>\u2212\/\u2212<jats:italic>; Gpx3<\/jats:italic>+\/\u2212<jats:italic>, Nkx3.1<\/jats:italic>\u2212\/\u2212<jats:italic>; Gpx3<\/jats:italic>\u2212\/\u2212 were produced. Randomly divided animals were weighed, and their genitourinary tract (GUT) weights were determined after euthanasia at 4, 8, and 12\u00a0months. The mRNA expression of the genes involved in oxidative stress and Wnt signaling was analyzed in the prostate. Histopathology, ROS, and superoxide dismutase (SOD) activities were also measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Loss of Gpx3 did not affect body weight and GUT weight in Nkx3.1 knockout mice. The mRNA expression of SOD3, iNOS, Hmox, and CISD2, which are associated with oxidative stress, was increased in Nkx3.1\u2212\/\u2212; Gpx3\u2212\/\u2212 mice at 4\u00a0months but decreased at 8 and 12\u00a0months. There was no change in \u03b2\u2010catenin and its targets associated with Wnt signaling. Increased ROS and decreased SOD activity were observed in Nkx3.1\u2212\/\u2212; Gpx3\u2212\/\u2212 mice at 12\u00a0months of age. The histopathologic score and epithelium thickness were increased, and lumen area was decreased in Gpx3 knockout mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and Conclusions<\/jats:title><jats:p><jats:italic>Gpx3<\/jats:italic> loss increased the hyperplasia of PIN in the pre\u2010cancerous stage of the prostate. Loss of <jats:italic>Gpx3<\/jats:italic> induced oxidative stress. Histopathologically, no invasive carcinoma was identified, and <jats:italic>Gpx3<\/jats:italic> loss did not increase Wnt\/\u03b2\u2010catenin signaling. Further research on the role of GPX3 in the transition of PIN to invasive carcinoma is needed. We show, for the first time, that the antioxidant enzyme GPX3 plays a vital role in inhibiting hyperplasia in the PIN stage of the prostate gland in vivo.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.12828","type":"journal-article","created":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T20:30:38Z","timestamp":1590438638000},"page":"1486-1493","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Loss of glutathione peroxidase 3 induces ROS and contributes to prostatic hyperplasia in <i>Nkx3.1<\/i> knockout mice"],"prefix":"10.1111","volume":"8","author":[{"given":"Ukjin","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Laboratory Animal Medicine Research Institute for Veterinary Science BK21 PLUS Program for Creative Veterinary Science Research College of Veterinary Medicine Seoul National University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u2010Yoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology School of Medicine Konkuk University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Min","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine Research Institute for Veterinary Science BK21 PLUS Program for Creative Veterinary Science Research College of Veterinary Medicine Seoul National University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bokyeong","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine Research Institute for Veterinary Science BK21 PLUS Program for Creative Veterinary Science Research College of Veterinary Medicine Seoul National University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine Research Institute for Veterinary Science BK21 PLUS Program for Creative Veterinary Science Research College of Veterinary Medicine Seoul National University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junpil","family":"Bang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine Research Institute for Veterinary Science BK21 PLUS Program for Creative Veterinary Science Research College of Veterinary Medicine Seoul National University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine Research Institute for Veterinary Science BK21 PLUS Program for Creative Veterinary Science Research College of Veterinary Medicine Seoul National University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4971-4640","authenticated-orcid":false,"given":"Jae\u2010Hak","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine Research Institute for Veterinary Science BK21 PLUS Program for Creative Veterinary Science Research College of Veterinary Medicine Seoul National University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,7,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21262"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21551"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2008.12.011"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2016.119"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1997.4715"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(00)00453-4"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-2688"},{"key":"e_1_2_8_9_1","first-page":"2411","article-title":"Analysis of 99 microdissected prostate carcinomas reveals a high frequency of allelic loss on chromosome 8p12\u201321","volume":"56","author":"Vocke CD","year":"1996","journal-title":"Cancer Res"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.8.966"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0177(2000)9999:9999<::AID-DVDY1054>3.0.CO;2-E"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.5.1495-1503.2002"},{"key":"e_1_2_8_13_1","first-page":"3886","article-title":"Nkx3.1; 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