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:
CreatorsEmailORCIDORCID Put Code
Tonnus, WulfUNSPECIFIEDorcid.org/0000-0002-9728-1413UNSPECIFIED
Maremonti, FrancescaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Belavgeni, AlexiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Latk, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brucker, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Maessenhausen, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meyer, ClaudiaUNSPECIFIEDorcid.org/0000-0002-8722-0772UNSPECIFIED
Locke, SophieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gembardt, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beer, KristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoppenz, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hugo, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anders, Hans-JoachimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bornstein, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shao, FengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Linkermann, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kusunoki, YoshihiroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, Jan U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
REGULATED CELL-DEATH; MIXED LINEAGE KINASE; MEDIATES NECROPTOSIS; NLRP3 INFLAMMASOME; MOLECULAR SWITCH; DOMAIN-LIKE; PROTEIN; PYROPTOSIS; NECROSIS; DISEASEMultiple languages
Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69086

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