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Article

Proteomic Analysis of Niemann-Pick Type C Hepatocytes Reveals Potential Therapeutic Targets for Liver Damage

1
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile
2
Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-8018, USA
3
Institute for Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, 53115 Bonn, Germany
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Laboratory of Cell Signaling, Department of Cellular and Molecular Biology, Biological Sciences Faculty, CARE UC, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile
5
Centro de Genética y Genómica, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago 7710162, Chile
*
Authors to whom correspondence should be addressed.
Academic Editor: Sheng Pan
Cells 2021, 10(8), 2159; https://doi.org/10.3390/cells10082159
Received: 29 July 2021 / Revised: 16 August 2021 / Accepted: 18 August 2021 / Published: 21 August 2021
(This article belongs to the Special Issue Deciphering the Proteome in Cell Biology and Diseases)
Niemann-Pick type C disease (NPCD) is a lysosomal storage disorder caused by mutations in the NPC1 gene. The most affected tissues are the central nervous system and liver, and while significant efforts have been made to understand its neurological component, the pathophysiology of the liver damage remains unclear. In this study, hepatocytes derived from wild type and Npc1−/− mice were analyzed by mass spectrometry (MS)-based proteomics in conjunction with bioinformatic analysis. We identified 3832 proteins: 416 proteins had a p-value smaller than 0.05, of which 37% (n = 155) were considered differentially expressed proteins (DEPs), 149 of them were considered upregulated, and 6 were considered downregulated. We focused the analysis on pathways related to NPC pathogenic mechanisms, finding that the most significant changes in expression levels occur in proteins that function in the pathways of liver damage, lipid metabolism, and inflammation. Moreover, in the group of DEPs, 30% (n = 47) were identified as lysosomal proteins and 7% (n = 10) were identified as mitochondrial proteins. Importantly, we found that lysosomal DEPs, including CTSB/D/Z, LIPA, DPP7 and GLMP, and mitocondrial DEPs, AKR1B10, and VAT1 had been connected with liver fibrosis, damage, and steatosis in previous studies, validiting our dataset. Our study found potential therapeutic targets for the treatment of liver damage in NPCD. View Full-Text
Keywords: liver damage; Niemann Pick type C disease; lysosomal storage disorder; proteomic analysis; mass spectrometry liver damage; Niemann Pick type C disease; lysosomal storage disorder; proteomic analysis; mass spectrometry
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MDPI and ACS Style

Balboa, E.; Marín, T.; Oyarzún, J.E.; Contreras, P.S.; Hardt, R.; van den Bosch, T.; Alvarez, A.R.; Rebolledo-Jaramillo, B.; Klein, A.D.; Winter, D.; Zanlungo, S. Proteomic Analysis of Niemann-Pick Type C Hepatocytes Reveals Potential Therapeutic Targets for Liver Damage. Cells 2021, 10, 2159. https://doi.org/10.3390/cells10082159

AMA Style

Balboa E, Marín T, Oyarzún JE, Contreras PS, Hardt R, van den Bosch T, Alvarez AR, Rebolledo-Jaramillo B, Klein AD, Winter D, Zanlungo S. Proteomic Analysis of Niemann-Pick Type C Hepatocytes Reveals Potential Therapeutic Targets for Liver Damage. Cells. 2021; 10(8):2159. https://doi.org/10.3390/cells10082159

Chicago/Turabian Style

Balboa, Elisa, Tamara Marín, Juan E. Oyarzún, Pablo S. Contreras, Robert Hardt, Thea van den Bosch, Alejandra R. Alvarez, Boris Rebolledo-Jaramillo, Andres D. Klein, Dominic Winter, and Silvana Zanlungo. 2021. "Proteomic Analysis of Niemann-Pick Type C Hepatocytes Reveals Potential Therapeutic Targets for Liver Damage" Cells 10, no. 8: 2159. https://doi.org/10.3390/cells10082159

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