{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T20:25:54Z","timestamp":1773692754725,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2008,6,20]],"date-time":"2008-06-20T00:00:00Z","timestamp":1213920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Proprotein convertase subtilisin\/kexin type 9 (PCSK9) is a key regulator of serum cholesterol. The possibility that PCSK9 also functions in other pathways needs to be addressed. We have transfected HepG2 cells with mutant D374Y\u2010PCSK9 or control vector. Gene expression signatures were determined using the Affymetrix GeneChip technology, and the expression pattern of selected genes was confirmed by quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR). Data was normalized and analyzed using a model\u2010based background adjustment for oligonucleotide expression arrays, then filtered based upon expression within treatments group, and subjected to moderated t\u2010statistics. Five hundred twenty transcripts had altered expression levels between D374Y\u2010PCSK9 and control vector. Among the 520 probes on our top list, 312 were found to have an assigned Gene Ontology (GO) term, and 96 were found in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Genome\u2010wide expression profiling revealed that \u201csteroid biosynthesis,\u201d \u201csterol metabolism,\u201d and \u201ccholesterol biosynthsis\u201d were affected by D374Y\u2010PCSK9. Also, the GO biological process terms \u201cresponse to stresss,\u201d \u201cresponse to virus,\u201d \u201cresponse to unfolded protein,\u201d and \u201cimmune response\u201d were influenced by D374Y\u2010PCSK9. Our results suggest that D374Y\u2010PCSK9 results in up\u2010regulation of genes involved in sterol biosynthesis and down\u2010regulation of stress\u2010response genes and specific inflammation pathways. J. Cell. Physiol. 217: 459\u2013467, 2008. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21519","type":"journal-article","created":{"date-parts":[[2008,6,20]],"date-time":"2008-06-20T13:58:30Z","timestamp":1213970310000},"page":"459-467","source":"Crossref","is-referenced-by-count":29,"title":["Genome\u2010wide expression analysis of cells expressing gain of function mutant D374Y\u2010PCSK9"],"prefix":"10.1002","volume":"217","author":[{"given":"Trine","family":"Ranheim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morten","family":"Mattingsdal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica M.","family":"Lindvall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00d8ystein L.","family":"Holla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Knut 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