A proteomic study of the regulatory role for STAT-1 in cytokine-induced beta-cell death

Dieter Rondas, Valborg Gudmundsdottir, Wannes D’Hertog, Inne Crèvecoeur, Etienne Waelkens, Søren Brunak, Chantal Mathieu, Lut Overbergh

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    PURPOSE: Signal transducer and activator of transcription 1 (STAT-1) plays a crucial role in cytokine-induced beta-cell destruction. However, its precise downstream pathways have not been completely clarified. We performed a proteome analysis of cytokine-exposed C57Bl/6 and STAT-1-/- mouse islets and prioritized proteins for their potential in relation to type 1 diabetes (T1D).
    EXPERIMENTAL DESIGN: Differential proteins were identified using a combination of 2D-DIGE and MALDI-TOF/TOF analysis and were subjected to ingenuity pathway analysis (IPA). Protein-protein interaction networks were created and a phenome-interactome ranking of the differential proteins based on their assignment to T1D was performed.
    RESULTS: Numerous STAT-1-regulated proteins were identified and divided in different groups according to their biological function. The largest group of proteins was the one involved in protein synthesis and processing. Network analysis revealed a complex interaction between proteins from different functional groups and IPA analysis confirmed the protective effect of STAT-1 deletion on cytokine-induced beta-cell death. Finally, a central role in this STAT-1-regulated mechanism was assigned to small ubiquitin-related modifier 4 (SUMO4).
    CONCLUSIONS AND CLINICAL RELEVANCE: These findings confirm a central role for STAT-1 in pancreatic islet inflammation induced destruction and most importantly elucidate the underlying proteomic pathways involved.
    Original languageEnglish
    JournalProteomics - Clinical Applications
    Volume9
    Issue number9-10
    Pages (from-to)938-952
    Number of pages15
    ISSN1862-8346
    DOIs
    Publication statusPublished - 2015

    Keywords

    • Beta-cell death
    • STAT-1
    • Type 1 diabetes

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