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Molecules 2019, 24(5), 994; https://doi.org/10.3390/molecules24050994

Differential Proteomics Reveals miR-155 as a Novel Indicator of Liver and Spleen Pathology in the Symptomatic Niemann-Pick Disease, Type C1 Mouse Model

1
Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, USA
2
Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20879, USA
3
Laboratory for Integrative Neuroscience, University of Illinois at Chicago, Chicago, IL 60607, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Zhenbin Zhang
Received: 1 February 2019 / Revised: 25 February 2019 / Accepted: 1 March 2019 / Published: 12 March 2019
(This article belongs to the Special Issue CZE/LC-MS-based Proteomics)
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Abstract

Niemann-Pick disease, type C1 (NPC1) is a rare, autosomal recessive, lipid storage disorder caused by mutations in NPC1. As a result, there is accumulation of unesterified cholesterol and sphingolipids in the late endosomal/lysosomal system. Clinically, patients can present with splenomegaly and hepatomegaly. In the current study, we analyzed the differential proteome of the spleen in symptomatic Npc1−/− mice to complement previous studies focused on the differential proteome of the liver, and then evaluated biomolecules that may serve as tissue biomarkers. The proteomic analysis revealed altered pathways in NPC1 representing different functional categories including heme synthesis, cellular regulation and phosphoinositide metabolism in both tissues. Differential proteins included several activators of the ubiquitous and critical protein, Akt, a major kinase involved in multiple cellular processes. Evaluation of Akt revealed decreased expression in both the liver and spleen tissues of symptomatic Npc1−/− mice. Upstream regulation analysis also suggested that miR-155 may modulate the differences of known downstream protein targets observed in our dataset. Upon evaluation of miR-155, we observed an increased expression in the liver and decreased expression in the spleen of symptomatic Npc1−/− mice. Here, we propose that miR-155 may be a novel indicator of spleen and liver pathology in NPC1. View Full-Text
Keywords: Niemann-Pick type C1; spleen proteomics; AJS-ESI mass spectrometry; lysosomal storage disorder; miR-155 Niemann-Pick type C1; spleen proteomics; AJS-ESI mass spectrometry; lysosomal storage disorder; miR-155
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Pergande, M.R.; Cougnoux, A.; Rathnayake, R.A.C.; Porter, F.D.; Cologna, S.M. Differential Proteomics Reveals miR-155 as a Novel Indicator of Liver and Spleen Pathology in the Symptomatic Niemann-Pick Disease, Type C1 Mouse Model. Molecules 2019, 24, 994.

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