| First Author | Leeds J | Year | 2020 |
| Journal | Am J Physiol Renal Physiol | Volume | 319 |
| Issue | 4 | Pages | F654-F663 |
| PubMed ID | 32715759 | Mgi Jnum | J:298438 |
| Mgi Id | MGI:6480118 | Doi | 10.1152/ajprenal.00064.2020 |
| Citation | Leeds J, et al. (2020) Protective role of DJ-1 in endotoxin-induced acute kidney injury. Am J Physiol Renal Physiol 319(4):F654-F663 |
| abstractText | Acute kidney injury (AKI) is a frequent complication of sepsis and an important cause of morbidity and mortality worldwide. A cornerstone of sepsis-associated AKI is dysregulated inflammation, leading to increased tissue oxidative stress and free radical formation, which leads to multiple forms of cell death. DJ-1 is a peroxiredoxin protein with multiple functions, including its ability to control cellular oxidative stress. Although DJ-1 is expressed prominently by renal tubules, its role in AKI has not been investigated. In the present study, we examined the effect of DJ-1 deficiency in a murine model of endotoxin-induced AKI. Endotoxemia induced greater kidney injury in DJ-1-deficient mice. Furthermore, DJ-1 deficiency increased renal oxidative stress associated with increased renal tubular apoptosis and with expression of death domain-associated protein (DAXX). Similar to the in vivo model, in vitro experiments using a medullary collecting duct cell line (mIMCD3) and cytotoxic serum showed that serum obtained from wild-type mice resulted in increased expression of s100A8/s100A9, DAXX, and apoptosis in DJ-1-deficient mIMCD3 cells. Our findings demonstrate a novel renal protective role for renal tubular DJ-1 during endotoxemia through control of oxidative stress, renal inflammation, and DAXX-dependent apoptosis. |
