| First Author | Cui P | Year | 2023 |
| Journal | Eur J Immunol | Volume | 53 |
| Issue | 10 | Pages | e2250071 |
| PubMed ID | 37379419 | Mgi Jnum | J:343664 |
| Mgi Id | MGI:7565938 | Doi | 10.1002/eji.202250071 |
| Citation | Cui P, et al. (2023) DsbA-L deletion attenuates LPS-induced acute kidney injury by modulating macrophage polarization. Eur J Immunol 53(10):e2250071 |
| abstractText | Disulfide bond A oxidoreductase-like protein (DsbA-L) drives acute kidney injury (AKI) by directly upregulating the expression of voltage-dependent anion-selective channels in proximal tubular cells. However, the role of DsbA-L in immune cells remains unclear. In this study, we used an LPS-induced AKI mouse model to assess the hypothesis that DsbA-L deletion attenuates LPS-induced AKI and explore the potential mechanism of DsbA-L action. After 24 hours of LPS exposure, the DsbA-L knockout group exhibited lower serum creatinine levels compared to the WT group. Furthermore, peripheral levels of the inflammatory cytokine IL-6 were decreased. Transcriptomic data analysis revealed a significant down-regulation in the IL-17 and tumor necrosis factor pathways in DsbA-L knockout mice following LPS induction. Metabolomic analysis suggested that arginine metabolism was significantly different between the WT and DsbA-L knockout groups after LPS treatment. Notably, the M1 polarization of macrophages in the kidneys of DsbA-L knockout AKI mice was significantly reduced. Expression of the transcription factors NF-kappaB and AP-1 was downregulated after DsbA-L knockout. Our results suggest that DsbA-L regulates LPS-mediated oxidative stress, promotes M1 polarization of macrophages, and induces expression of inflammatory factors via the NF-kappaB/AP-1 pathway. |
