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Tonnus, W.* ; Maremonti, F.* ; Belavgeni, A.* ; Latk, M.* ; Brucker, A.J.* ; von Maessenhausen, A.* ; Meyer, C.* ; Locke, S.* ; Gembardt, F.* ; Beer, K.* ; Hoppenz, P.* ; Hugo, C.* ; Anders, H.J.* ; Bornstein, S.R. ; Shao, F.W.* ; Linkermann, A.*

Gasdermin D-deficient mice are hypersensitive to acute kidney injury.

Cell Death Dis. 13:792 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Signaling pathways of regulated necrosis, such as necroptosis and ferroptosis, contribute to acute kidney injury (AKI), but the role of pyroptosis is unclear. Pyroptosis is mediated by the pore-forming protein gasdermin D (GSDMD). Here, we report a specific pattern of GSDMD-protein expression in the peritubular compartment of mice that underwent bilateral ischemia and reperfusion injury (IRI). Along similar lines, the GSDMD-protein expression in whole kidney lysates increased during the first 84 h following cisplatin-induced AKI. Importantly, unlike whole kidney lysates, no GSDMD-protein expression was detectable in isolated kidney tubules. In IRI and cisplatin-induced AKI, GSDMD-deficient mice exhibited hypersensitivity to injury as assessed by tubular damage, elevated markers of serum urea, and serum creatinine. This hypersensitivity was reversed by a combined deficiency of GSDMD and the necroptosis mediator mixed lineage kinase domain-like (MLKL). In conclusion, we demonstrate a non-cell autonomous role for GSDMD in protecting the tubular compartment from necroptosis-mediated damage in IRI.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 2041-4889
e-ISSN 2041-4889
Zeitschrift Cell Death & Disease
Quellenangaben Band: 13, Heft: 9, Seiten: , Artikelnummer: 792 Supplement: ,
Verlag Nature Publishing Group
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)
Förderungen Deutsche Forschungsgemeinschaft (German Research Foundation)