| First Author | Miao N | Year | 2019 |
| Journal | Kidney Int | Volume | 96 |
| Issue | 5 | Pages | 1105-1120 |
| PubMed ID | 31405732 | Mgi Jnum | J:297425 |
| Mgi Id | MGI:6472667 | Doi | 10.1016/j.kint.2019.04.035 |
| Citation | Miao N, et al. (2019) The cleavage of gasdermin D by caspase-11 promotes tubular epithelial cell pyroptosis and urinary IL-18 excretion in acute kidney injury. Kidney Int 96(5):1105-1120 |
| abstractText | Inflammation and tubular cell death are the hallmarks of acute kidney injury. However, the precise mechanism underlying these effects has not been fully elucidated. Here we tested whether caspase-11, an inflammatory member of the caspase family, was increased in cisplatin or ischemia-reperfusion-induced acute kidney injury. Caspase-11 knockout mice after cisplatin treatment exhibited attenuated deterioration of renal functional, reduced tubular damage, reduced macrophage and neutrophil infiltration, and decreased urinary IL-18 excretion. Mechanistically, the upregulation of caspase-11 by either cisplatin or ischemia-reperfusion cleaved gasdermin D (GSDMD) into GSDMD-N, which translocated onto the plasma membrane, thus triggering cell pyroptosis and facilitated IL-18 release in primary cultured renal tubular cells. These results were further confirmed in GSDMD knockout mice that cisplatin-induced renal morphological and functional deterioration as well as urinary IL-18 excretion were alleviated. Furthermore, deficiency of GSDMD significantly suppressed cisplatin-induced IL-18 release but not the transcription and maturation level of IL-18 in tubular cells. Thus, our study indicates that caspase-11/GSDMD dependent tubule cell pyroptosis plays a significant role in initiating tubular cell damage, urinary IL-18 excretion and renal functional deterioration in acute kidney injury. |
