{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:50:34Z","timestamp":1792799434545,"version":"4.5.0"},"reference-count":73,"publisher":"American Society for Clinical Investigation","issue":"11","funder":[{"name":"NWO-ALW","award":["817.02.022"],"award-info":[{"award-number":["817.02.022"]}]},{"name":"EU FP7","award":["TransCard (FP7-603091-2)"],"award-info":[{"award-number":["TransCard (FP7-603091-2)"]}]},{"name":"the Dutch heart foundation","award":["CVON 2017-20"],"award-info":[{"award-number":["CVON 2017-20"]}],"id":[{"id":"https:\/\/ror.org\/05nxhgm70","id-type":"ROR","asserted-by":"crossref"}]},{"name":"dutch heart foundation","award":["2015T068"],"award-info":[{"award-number":["2015T068"]}],"id":[{"id":"https:\/\/ror.org\/05nxhgm70","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,6,6]]},"abstract":"<jats:p>\n                    The evolutionary conserved Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex is one of the crucial multiprotein complexes that facilitates endosomal recycling of transmembrane proteins. Defects in WASH components have been associated with inherited developmental and neurological disorders in humans. Here, we show that hepatic ablation of the WASH component\n                    <jats:italic>Washc1<\/jats:italic>\n                    in chow-fed mice increases plasma concentrations of cholesterol in both LDLs and HDLs, without affecting hepatic cholesterol content, hepatic cholesterol synthesis, biliary cholesterol excretion, or hepatic bile acid metabolism. Elevated plasma LDL cholesterol was related to reduced hepatocytic surface levels of the LDL receptor (LDLR) and the LDLR-related protein LRP1. Hepatic WASH ablation also reduced the surface levels of scavenger receptor class B type I and, concomitantly, selective uptake of HDL cholesterol into the liver. Furthermore, we found that WASHC1 deficiency increases LDLR proteolysis by the inducible degrader of LDLR, but does not affect proprotein convertase subtilisin\/kexin type 9\u2013mediated LDLR degradation. Remarkably, however, loss of hepatic WASHC1 may sensitize LRP1 for proprotein convertase subtilisin\/kexin type 9\u2013induced degradation. Altogether, these findings identify the WASH complex as a regulator of LDL as well as HDL metabolism and provide in vivo evidence for endosomal trafficking of scavenger receptor class B type I in hepatocytes.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.126462","type":"journal-article","created":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T11:01:16Z","timestamp":1559732476000},"source":"Crossref","is-referenced-by-count":39,"title":["The hepatic WASH complex is required for efficient plasma LDL and HDL cholesterol clearance"],"prefix":"10.1172","volume":"4","author":[{"given":"Melinde","family":"Wijers","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Zanoni","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry, University Hospital Zurich, Zurich, 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