{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:42:05Z","timestamp":1778874125891,"version":"3.51.4"},"reference-count":50,"publisher":"Portland Press Ltd.","issue":"2","license":[{"start":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T00:00:00Z","timestamp":1578960000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,1,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Circulating factors have been implicated in the pathogenesis of minimal change disease (MCD), and may have direct effects on cholesterol metabolism. This study investigated the pathogenesis of hypercholesterolemia in an IL-13 overexpression rat model of MCD prior to the onset of proteinuria, so as to establish the direct contribution of IL-13, especially with regard to hepatic cholesterol handling. In this model of MCD, the temporal relationship between hypercholesterolemia and proteinuria was first identified. Plasma proprotein convertase subtilisin\/kexin type 9 (Pcsk9) and liver ATP-binding cassette sub-family G member 5 (Abcg5) were measured using ELISA. Liver Ldlr and liver X receptor alpha (Lxra) were quantified with Western blot. Abcg5-mediated cholesterol efflux in IL-13-stimulated rat primary hepatocytes was measured using taurocholate as cholesterol acceptor. The role of Lxra was validated using a luciferase assay in Lxre-luciferase-transfected IL-13-stimulated hepatocytes. IL-13-transfected rats developed hypercholesterolemia prior to proteinuria, with 35% of rats hypercholesterolemic but only 11% proteinuric by Day 20 (P = 0.04). These pre-proteinuric hypercholesterolemic rats showed elevations in total and LDL-cholesterol, but not hypertriglyceridemia or hepatic steatosis. The hypercholesterolemia was associated with increased hepatic Pcsk9 synthesis and enhanced circulating Pcsk9 levels, which correlated strongly with plasma total cholesterol (r = 0.73, P&amp;lt;0.001). The hypercholesterolemia was also contributed by decreased Abcg5 expression and activity, due to reduced Lxra expression. Lxra expression correlated with plasma total cholesterol levels (r = \u22120.52, P = 0.01), and overexpression of pLxra in rat hepatocytes abrogated the IL-13-mediated down-regulation of Lxre-driven gene expression. In conclusion, we have shown that IL-13 induced changes in hepatic cholesterol handling in a cytokine-induced rat model of MCD, resulting in hypercholesterolemia which can precede the onset of proteinuria.<\/jats:p>","DOI":"10.1042\/cs20190961","type":"journal-article","created":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T11:49:45Z","timestamp":1579002585000},"page":"225-237","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["IL-13-driven alterations in hepatic cholesterol handling contributes to hypercholesterolemia in a rat model of minimal change disease"],"prefix":"10.1042","volume":"134","author":[{"given":"Lauretta\u00a0D.","family":"Low","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore"},{"name":"Khoo Teck Puat-National University Children\u2019s Medical Institute, National University Health System, Singapore 119260, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangjian","family":"Lu","sequence":"additional","affiliation":[{"name":"Khoo Teck Puat-National University Children\u2019s Medical Institute, National University Health System, Singapore 119260, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5841-1417","authenticated-orcid":false,"given":"Chang-Yien","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore"},{"name":"Khoo Teck Puat-National University Children\u2019s Medical Institute, National University Health System, Singapore 119260, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinmiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Bioinformatics, Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry\u00a0H.","family":"Yang","sequence":"additional","affiliation":[{"name":"Cancer Science Institute of Singapore & Department of Biochemistry, National University of Singapore, Singapore 117599, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanry","family":"Yu","sequence":"additional","affiliation":[{"name":"Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore"},{"name":"Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore"},{"name":"Institute of Bioengineering and Nanotechnology (IBN), Agency for Science, Technology and Research, Singapore 138669, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline\u00a0G.L.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kar-Hui","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore"},{"name":"Khoo Teck Puat-National University Children\u2019s Medical Institute, National University Health System, Singapore 119260, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6008-382X","authenticated-orcid":false,"given":"Hui-Kim","family":"Yap","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore"},{"name":"Khoo Teck Puat-National University Children\u2019s Medical Institute, National University Health System, Singapore 119260, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2020,1,27]]},"reference":[{"key":"2021113012343021700_B1","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/S0140-6736(03)14184-0","article-title":"Nephrotic syndrome in childhood","volume":"362","author":"Eddy","year":"2003","journal-title":"Lancet"},{"key":"2021113012343021700_B2","doi-asserted-by":"publisher","first-page":"372","DOI":"10.5414\/CNP74372","article-title":"The changing pattern of primary glomerulonephritis in Singapore and other countries over the past 3 decades","volume":"74","author":"Woo","year":"2010","journal-title":"Clin. 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