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Glycosylation Analysis of Urinary Peptidome Highlights IGF2 Glycopeptides in Association with CKD.
Lohia, Sonnal; Latosinska, Agnieszka; Zoidakis, Jerome; Makridakis, Manousos; Mischak, Harald; Glorieux, Griet; Vlahou, Antonia; Jankowski, Vera.
Afiliación
  • Lohia S; Center of Systems Biology, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece.
  • Latosinska A; Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, 52074 Aachen, Germany.
  • Zoidakis J; Mosaiques Diagnostics GmbH, 30659 Hannover, Germany.
  • Makridakis M; Center of Systems Biology, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece.
  • Mischak H; Center of Systems Biology, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece.
  • Glorieux G; Mosaiques Diagnostics GmbH, 30659 Hannover, Germany.
  • Vlahou A; Department of Internal Medicine and Pediatrics, Nephrology Division, Ghent University Hospital, 9000 Gent, Belgium.
  • Jankowski V; Center of Systems Biology, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece.
Int J Mol Sci ; 24(6)2023 Mar 11.
Article en En | MEDLINE | ID: mdl-36982475
Chronic kidney disease (CKD) is prevalent in 10% of world's adult population. The role of protein glycosylation in causal mechanisms of CKD progression is largely unknown. The aim of this study was to identify urinary O-linked glycopeptides in association to CKD for better characterization of CKD molecular manifestations. Urine samples from eight CKD and two healthy subjects were analyzed by CE-MS/MS and glycopeptides were identified by a specific software followed by manual inspection of the spectra. Distribution of the identified glycopeptides and their correlation with Age, eGFR and Albuminuria were evaluated in 3810 existing datasets. In total, 17 O-linked glycopeptides from 7 different proteins were identified, derived primarily from Insulin-like growth factor-II (IGF2). Glycosylation occurred at the surface exposed IGF2 Threonine 96 position. Three glycopeptides (DVStPPTVLPDNFPRYPVGKF, DVStPPTVLPDNFPRYPVG and DVStPPTVLPDNFPRYP) exhibited positive correlation with Age. The IGF2 glycopeptide (tPPTVLPDNFPRYP) showed a strong negative association with eGFR. These results suggest that with aging and deteriorating kidney function, alterations in IGF2 proteoforms take place, which may reflect changes in mature IGF2 protein. Further experiments corroborated this hypothesis as IGF2 increased plasma levels were observed in CKD patients. Protease predictions, considering also available transcriptomics data, suggest activation of cathepsin S with CKD, meriting further investigation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glicopéptidos / Insuficiencia Renal Crónica / Espectrometría de Masas en Tándem Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Grecia Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glicopéptidos / Insuficiencia Renal Crónica / Espectrometría de Masas en Tándem Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Grecia Pais de publicación: Suiza