Slaats, Gisela G., Braun, Fabian ORCID: 0000-0002-4742-050X, Hoehne, Martin, Frech, Laura E., Blomberg, Linda, Benzing, Thomas, Schermer, Bernhard ORCID: 0000-0002-5194-9000, Rinschen, Markus M. and Kurschat, Christine E. (2018). Urine-derived cells: a promising diagnostic tool in Fabry disease patients. Sci Rep, 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

Fabry disease is a lysosomal storage disorder resulting from impaired alpha-galactosidase A (alpha-Gal A) enzyme activity due to mutations in the GLA gene. Currently, powerful diagnostic tools and in vivo research models to study Fabry disease are missing, which is a major obstacle for further improvements in diagnosis and therapy. Here, we explore the utility of urine-derived primary cells of Fabry disease patients. Viable cells were isolated and cultured from fresh urine void. The obtained cell culture, modeling the renal epithelium, is characterized by patient-specific information. We demonstrate that this non-invasive source of patient cells provides an adequate cellular in vivo model as cells exhibit decreased alpha-Gal A enzyme activity and concomitant globotriaosylceramide accumulation. Subsequent quantitative proteomic analyses revealed dysregulation of endosomal and lysosomal proteins indicating an involvement of the Coordinated Lysosomal Expression and Regulation (CLEAR) network in the disease pathology. This proteomic pattern resembled data from our previously described human podocyte model of Fabry disease. Taken together, the employment of urine-derived primary cells of Fabry disease patients might have diagnostic and prognostic implications in the future. Our findings pave the way towards a more detailed understanding of pathophysiological mechanisms and may allow the development of future tailored therapeutic strategies.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Slaats, Gisela G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Braun, FabianUNSPECIFIEDorcid.org/0000-0002-4742-050XUNSPECIFIED
Hoehne, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frech, Laura E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blomberg, LindaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benzing, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schermer, BernhardUNSPECIFIEDorcid.org/0000-0002-5194-9000UNSPECIFIED
Rinschen, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kurschat, Christine E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-179578
DOI: 10.1038/s41598-018-29240-w
Journal or Publication Title: Sci Rep
Volume: 8
Date: 2018
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2045-2322
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
QUANTITATIVE PROTEOMICS; REPLACEMENT THERAPY; ALPHA-GALACTOSIDASE; JOUBERT SYNDROME; QUANTIFICATION; TFEB; GLOBOTRIAOSYLCERAMIDE; IDENTIFICATION; HETEROZYGOTES; PURIFICATIONMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/17957

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