King's College London

Research portal

Gasdermin D-deficient mice are hypersensitive to acute kidney injury

Research output: Contribution to journalArticlepeer-review

Wulf Tonnus, Francesca Maremonti, Alexia Belavgeni, Markus Latk, Yoshihiro Kusunoki, Anne Brucker, Anne von Mässenhausen, Claudia Meyer, Sophie Locke, Florian Gembardt, Kristina Beer, Paul Hoppenz, Jan U. Becker, Christian Hugo, Hans Joachim Anders, Stefan R. Bornstein, Feng Shao, Andreas Linkermann

Original languageEnglish
Article number792
JournalCell Death and Disease
Issue number9
PublishedSep 2022

Bibliographical note

Funding Information: Work in the Linkermann Lab is funded by the German Research Foundation (DFG), SFB-TRR 205, SFB-TRR 127, SPP 2306, IRTG 2251, and a Heisenberg-Professorship to AL (project number 324141047). HJA was supported by the Deutsche Forschungsgemeinschaft (AN372/16-2, 27-1, and 30-1) Funding Information: We would like to cordially thank Romy Opitz, Anne Pioch, and Céline Laqua for expert technical assistance. We thank the Light Microscopy Facility at Dresden BIOTEC, in particular Hella Hartmann, and the histology facility at the CMCB of the TU Dresden with special acknowledgement of Susanne Weiche and Dana Thatmeyer for expert help. Publisher Copyright: © 2022, The Author(s).

King's Authors


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.

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454