| First Author | Tonnus W | Year | 2022 |
| Journal | Cell Death Dis | Volume | 13 |
| Issue | 9 | Pages | 792 |
| PubMed ID | 36109515 | Mgi Jnum | J:330852 |
| Mgi Id | MGI:7342202 | Doi | 10.1038/s41419-022-05230-9 |
| Citation | Tonnus W, et al. (2022) Gasdermin D-deficient mice are hypersensitive to acute kidney injury. Cell Death Dis 13(9):792 |
| abstractText | 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. |
