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Schömig, Thomas; Diefenhardt, Paul; Plagmann, Ingo; Trinsch, Bastian; Merz, Tim; Crispatzu, Giuliano; Unnersjö-Jess, David; Nies, Jasper; Pütz, David; Sierra Gonzalez, Claudio; Schermer, Bernhard; Benzing, Thomas; Brinkkoetter, Paul Thomas; Brähler, Sebastian

The podocytes’ inflammatory responses in experimental GN are independent of canonical MYD88-dependent toll-like receptor signaling

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  • Medientyp: E-Artikel
  • Titel: The podocytes’ inflammatory responses in experimental GN are independent of canonical MYD88-dependent toll-like receptor signaling
  • Beteiligte: Schömig, Thomas; Diefenhardt, Paul; Plagmann, Ingo; Trinsch, Bastian; Merz, Tim; Crispatzu, Giuliano; Unnersjö-Jess, David; Nies, Jasper; Pütz, David; Sierra Gonzalez, Claudio; Schermer, Bernhard; Benzing, Thomas; Brinkkoetter, Paul Thomas; Brähler, Sebastian
  • Erschienen: Springer Science and Business Media LLC, 2024
  • Erschienen in: Scientific Reports
  • Sprache: Englisch
  • DOI: 10.1038/s41598-024-52565-8
  • ISSN: 2045-2322
  • Schlagwörter: Multidisciplinary
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Podocytes form the kidney filtration barrier and continuously adjust to external stimuli to preserve their integrity even in the presence of inflammation. It was suggested that canonical toll-like receptor signaling, mediated by the adaptor protein MYD88, plays a crucial role in initiating inflammatory responses in glomerulonephritis (GN). We explored the influence of podocyte-intrinsic MYD88 by challenging wild-type (WT) and podocyte-specific <jats:italic>Myd88</jats:italic> knockout (MyD88<jats:sup>pko</jats:sup>) mice, with a model of experimental GN (nephrotoxic nephritis, NTN). Next-generation sequencing revealed a robust upregulation of inflammatory pathways and changes in cytoskeletal and cell adhesion proteins in sorted podocytes from WT mice during disease. Unchallenged MyD88<jats:sup>pko</jats:sup> mice were healthy and showed no proteinuria, normal kidney function and lacked morphological changes. During NTN, MyD88<jats:sup>pko</jats:sup> exhibited a transient increase in proteinuria in comparison to littermates, while histological damage, podocyte ultrastructure in STED imaging and frequencies of infiltrating immune cells by flow cytometry were unchanged. MYD88-deficiency led to subtle changes in the podocyte transcriptome, without a significant impact on the overall podocyte response to inflammation, presumably through MYD88-independent signaling pathways. In conclusion, our study reveals a comprehensive analysis of podocyte adaptation to an inflammatory environment on the transcriptome level, while MYD88-deficiency had only limited impact on the course of GN suggesting additional signaling through MYD88-independent signaling.</jats:p>
  • Zugangsstatus: Freier Zugang