| First Author | Wu X | Year | 2023 |
| Journal | FASEB J | Volume | 37 |
| Issue | 2 | Pages | e22738 |
| PubMed ID | 36583727 | Mgi Jnum | J:338746 |
| Mgi Id | MGI:7514463 | Doi | 10.1096/fj.202201400R |
| Citation | Wu X, et al. (2023) Vitamin D-vitamin D receptor alleviates oxidative stress in ischemic acute kidney injury via upregulating glutathione peroxidase 3. FASEB J 37(2):e22738 |
| abstractText | Vitamin D receptor was previously reported to be protective in acute kidney injury (AKI) with the mechanism unclear, while the role of renal localized glutathione peroxidase 3 (GPX3) was not illustrated. The present study aims to investigate the role of GPX3 as well as its correlation with vitamin D-vitamin D receptor (VD-VDR) in ischemia-reperfusion (I/R)-induced renal oxidative stress injury. We showed that the expression of GPX3 and VDR were consistently decreased in renal tissues of I/R-related AKI patients and mice models. VDR agonist paricalcitol could reverse GPX3 expression and inhibit oxidative stress in I/R mice or hypoxia-reoxygenation (H/R) insulted HK-2 cells. VDR deficiency resulted in aggregated oxidative stress and severer renal injury accompanied by further decreased renal GPX3, while tubular-specific VDR overexpression remarkably reduced I/R-induced renal injury with recovered GPX3 in mice. Neither serum selenium nor selenoprotein P was affected by paricalcitol administration nor Vdr modification in vivo. In addition, inhibiting GPX3 abrogated the protective effects of VD-VDR in HK-2 cells, while GPX3 overexpression remarkably attenuated H/R-induced oxidative stress and apoptosis. Mechanistic probing revealed the GPX3 as a VDR transcriptional target. Our present work revealed that loss of renal GPX3 may be a hallmark that promotes renal oxidative stress injury and VD-VDR could protect against I/R-induced renal injury via inhibition of oxidative stress partly by trans-regulating GPX3. In addition, maintenance of renal GPX3 could be a therapeutic strategy for ischemic AKI. |
