{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:12:58Z","timestamp":1790475178682,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,2,2]],"date-time":"2017-02-02T00:00:00Z","timestamp":1485993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diabetic nephropathy is the leading cause of end\u2010stage renal disease. Diabetic patients have increased plasma concentrations of apolipoprotein C\u2010I (<jats:styled-content style=\"fixed-case\">apoCI<\/jats:styled-content>), and meta\u2010analyses found that a polymorphism in <jats:italic><jats:styled-content style=\"fixed-case\">APOC1<\/jats:styled-content><\/jats:italic> is associated with an increased risk of developing nephropathy. To investigate whether overexpressing <jats:styled-content style=\"fixed-case\">apoCI<\/jats:styled-content> contributes to the development of kidney damage, we studied renal tissue and peritoneal macrophages from <jats:italic><jats:styled-content style=\"fixed-case\">APOC1<\/jats:styled-content><\/jats:italic> transgenic (<jats:italic><jats:styled-content style=\"fixed-case\">APOC1<\/jats:styled-content>\u2010<\/jats:italic>tg) mice and wild\u2010type littermates. In addition, we examined renal material from autopsied diabetic patients with and without diabetic nephropathy and from autopsied control subjects. We found that <jats:italic><jats:styled-content style=\"fixed-case\">APOC1<\/jats:styled-content><\/jats:italic>\u2010tg mice, but not wild\u2010type mice, develop albuminuria, renal dysfunction, and glomerulosclerosis with increased numbers of glomerular <jats:styled-content style=\"fixed-case\">M1<\/jats:styled-content> macrophages. Moreover, compared to wild\u2010type macrophages, stimulated macrophages isolated from <jats:italic><jats:styled-content style=\"fixed-case\">APOC1<\/jats:styled-content><\/jats:italic>\u2010tg mice have increased cytokine expression, including <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010alpha and <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010beta, both of which are known to increase the production of extracellular matrix proteins in mesangial cells. These results suggest that <jats:italic><jats:styled-content style=\"fixed-case\">APOC1<\/jats:styled-content><\/jats:italic> expression induces glomerulosclerosis, potentially by increasing the cytokine response in macrophages. Furthermore, we detected <jats:styled-content style=\"fixed-case\">apoCI<\/jats:styled-content> in the kidneys of diabetic patients, but not in control kidneys. Moreover, patients with diabetic nephropathy have significantly more <jats:styled-content style=\"fixed-case\">apoCI<\/jats:styled-content> present in glomeruli compared to diabetic patients without nephropathy, suggesting that <jats:styled-content style=\"fixed-case\">apoCI<\/jats:styled-content> could be involved in the development of diabetic nephropathy. <jats:styled-content style=\"fixed-case\">ApoCI<\/jats:styled-content> co\u2010localized with macrophages. Therefore, <jats:styled-content style=\"fixed-case\">apoCI<\/jats:styled-content> is a promising new therapeutic target for patients at risk of developing nephropathy. Copyright \u00a9 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4859","type":"journal-article","created":{"date-parts":[[2016,12,16]],"date-time":"2016-12-16T23:57:51Z","timestamp":1481932671000},"page":"589-599","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Apolipoprotein C\u2010I plays a role in the pathogenesis of glomerulosclerosis"],"prefix":"10.1002","volume":"241","author":[{"given":"Pascal","family":"Bus","sequence":"first","affiliation":[{"name":"Department of Pathology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Pierneef","sequence":"additional","affiliation":[{"name":"Department of Pathology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalie","family":"Bor","sequence":"additional","affiliation":[{"name":"Department of 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