Schömig, Thomas 
ORCID: 0009-0001-7560-4285, Diefenhardt, Paul ORCID: 0000-0003-3982-8983, Plagmann, Ingo ORCID: 0000-0003-0263-7040, Trinsch, Bastian ORCID: 0000-0003-4435-3214, Merz, Tim, Crispatzu, Giuliano ORCID: 0000-0001-8041-2125, Unnersjö-Jess, David ORCID: 0000-0002-4162-0973, Nies, Jasper ORCID: 0000-0003-3751-4008, Pütz, David, Sierra Gonzalez, Claudio ORCID: 0000-0002-8458-0377, Schermer, Bernhard ORCID: 0000-0002-5194-9000, Benzing, Thomas ORCID: 0000-0003-0512-1066, Brinkkoetter, Paul Thomas ORCID: 0000-0002-4287-2080 and Brähler, Sebastian ORCID: 0000-0002-7685-5780
(2024).
The podocytes’ inflammatory responses in experimental GN are independent of canonical MYD88-dependent toll-like receptor signaling.
Scientific Reports, 14 (1).
pp. 1-12.
Springer Nature.
ISSN 2045-2322
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Abstract
[Artikel-Nr.: 2292] 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 Myd88 knockout (MyD88pko) 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 MyD88pko mice were healthy and showed no proteinuria, normal kidney function and lacked morphological changes. During NTN, MyD88pko 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.
| Item Type: | Article |
| Creators: | Creators Email ORCID ORCID Put Code Merz, Tim UNSPECIFIED UNSPECIFIED UNSPECIFIED Pütz, David UNSPECIFIED UNSPECIFIED UNSPECIFIED |
| URN: | urn:nbn:de:hbz:38-815116 |
| Identification Number: | 10.1038/s41598-024-52565-8 |
| Journal or Publication Title: | Scientific Reports |
| Volume: | 14 |
| Number: | 1 |
| Page Range: | pp. 1-12 |
| Number of Pages: | 12 |
| Date: | 27 January 2024 |
| Publisher: | Springer Nature |
| ISSN: | 2045-2322 |
| Language: | English |
| Faculty: | Faculty of Medicine |
| Divisions: | CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Medicine > Innere Medizin > Klinik II für Innere Medizin - Nephrologie, Rheumatologie, Diabetologie und Allgemeine Innere Medizin Zentrum für Molekulare Medizin |
| Subjects: | Medical sciences Medicine |
| ['eprint_fieldname_oa_funders' not defined]: | Publikationsfonds UzK |
| Refereed: | Yes |
| URI: | http://kups.ub.uni-koeln.de/id/eprint/81511 |
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