Universität zu Köln

Tonnus, Wulf ORCID: 0000-0002-9728-1413, Maremonti, Francesca, Belavgeni, Alexia, Latk, Markus, Brucker, Anne, von Maessenhausen, Anne, Meyer, Claudia ORCID: 0000-0002-8722-0772, Locke, Sophie, Gembardt, Florian, Beer, Kristina, Hoppenz, Paul, Hugo, Christian, Anders, Hans-Joachim, Bornstein, Stefan, Shao, Feng, Linkermann, Andreas, Kusunoki, Yoshihiro and Becker, Jan U. (2022). Gasdermin D-deficient mice are hypersensitive to acute kidney injury. Cell Death Dis., 13 (9). LONDON: SPRINGERNATURE. ISSN 2041-4889

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tonnus, Wulf UNSPECIFIED orcid.org/0000-0002-9728-1413 UNSPECIFIED Maremonti, Francesca UNSPECIFIED UNSPECIFIED UNSPECIFIED Belavgeni, Alexia UNSPECIFIED UNSPECIFIED UNSPECIFIED Latk, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Brucker, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED von Maessenhausen, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyer, Claudia UNSPECIFIED orcid.org/0000-0002-8722-0772 UNSPECIFIED Locke, Sophie UNSPECIFIED UNSPECIFIED UNSPECIFIED Gembardt, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Beer, Kristina UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoppenz, Paul UNSPECIFIED UNSPECIFIED UNSPECIFIED Hugo, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Anders, Hans-Joachim UNSPECIFIED UNSPECIFIED UNSPECIFIED Bornstein, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Shao, Feng UNSPECIFIED UNSPECIFIED UNSPECIFIED Linkermann, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Kusunoki, Yoshihiro UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Jan U. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-690860
DOI:	10.1038/s41419-022-05230-9
Journal or Publication Title:	Cell Death Dis.
Volume:	13
Number:	9
Date:	2022
Publisher:	SPRINGERNATURE
Place of Publication:	LONDON
ISSN:	2041-4889
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language REGULATED CELL-DEATH; MIXED LINEAGE KINASE; MEDIATES NECROPTOSIS; NLRP3 INFLAMMASOME; MOLECULAR SWITCH; DOMAIN-LIKE; PROTEIN; PYROPTOSIS; NECROSIS; DISEASE Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69086