000046972 001__ 46972
000046972 005__ 20200221144126.0
000046972 0247_ $$2doi$$a10.1371/journal.pone.0147208
000046972 0248_ $$2sideral$$a93435
000046972 037__ $$aART-2016-93435
000046972 041__ $$aeng
000046972 100__ $$aMarques, A.R.A.
000046972 245__ $$aGpnmb is a potential marker for the visceral pathology in Niemann-Pick type C disease
000046972 260__ $$c2016
000046972 5060_ $$aAccess copy available to the general public$$fUnrestricted
000046972 5203_ $$aImpaired function of NPC1 or NPC2 lysosomal proteins leads to the intracellular accumulation of unesterified cholesterol, the primary defect underlying Niemann-Pick type C (NPC) disease. In addition, glycosphingolipids (GSLs) accumulate in lysosomes as well. Intralysosomal lipid accumulation triggers the activation of a set of genes, including potential biomarkers. Transcript levels of Gpnmb have been shown to be elevated in various tissues of an NPC mouse model. We speculated that Gpnmb could serve as a marker for visceral lipid accumulation in NPC disease. We report that Gpnmb expression is increased at protein level in macrophages in the viscera of Npc1nih/nih mice. Interestingly, soluble Gpnmb was also found to be increased in murine and NPC patient plasma. Exposure of RAW264.7 macrophages to the NPC-phenotype-inducing drug U18666A also upregulated Gpnmb expression. Inhibition of GSL synthesis with the glucosylceramide synthase (GCS) inhibitor N-butyl-1-deoxynojirimycin prevented U18666A-induced Gpnmb induction and secretion. In summary, we show that Gpnmb is upregulated in NPC mice and patients, most likely due to GSL accumulation.
000046972 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000046972 590__ $$a2.806$$b2016
000046972 591__ $$aMULTIDISCIPLINARY SCIENCES$$b15 / 63 = 0.238$$c2016$$dQ1$$eT1
000046972 592__ $$a1.236$$b2016
000046972 593__ $$aAgricultural and Biological Sciences (miscellaneous)$$c2016$$dQ1
000046972 593__ $$aMedicine (miscellaneous)$$c2016$$dQ1
000046972 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2016$$dQ1
000046972 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000046972 700__ $$aGabriel, T.L.
000046972 700__ $$aAten, J.
000046972 700__ $$aVan Roomen, C.P.A.A.
000046972 700__ $$aOttenhoff, R.
000046972 700__ $$aClaessen, N.
000046972 700__ $$aAlfonso, P.
000046972 700__ $$0(orcid)0000-0003-3392-7200$$aIrún, P.
000046972 700__ $$aGiraldo, P.
000046972 700__ $$aAerts, J.M.F.G.
000046972 700__ $$aVan Eijk, M.
000046972 773__ $$g11, 1 (2016), 0147208 [19 pp]$$pPLoS One$$tPloS one$$x1932-6203
000046972 8564_ $$s1315156$$uhttps://zaguan.unizar.es/record/46972/files/texto_completo.pdf$$yVersión publicada
000046972 8564_ $$s100159$$uhttps://zaguan.unizar.es/record/46972/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000046972 909CO $$ooai:zaguan.unizar.es:46972$$particulos$$pdriver
000046972 951__ $$a2020-02-21-13:03:38
000046972 980__ $$aARTICLE