| First Author | Yoo JY | Year | 2020 |
| Journal | Cell Rep | Volume | 33 |
| Issue | 3 | Pages | 108245 |
| PubMed ID | 33086058 | Mgi Jnum | J:298830 |
| Mgi Id | MGI:6489062 | Doi | 10.1016/j.celrep.2020.108245 |
| Citation | Yoo JY, et al. (2020) LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1. Cell Rep 33(3):108245 |
| abstractText | Cytosolic proteins are required for regulation of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (Nox) isozymes. Here we show that Src homology 3 (SH3) domain-containing YSC84-like 1 (SH3YL1), as a Nox4 cytosolic regulator, mediates lipopolysaccharide (LPS)-induced H2O2 generation, leading to acute kidney injury. The SH3YL1, Ysc84p/Lsb4p, Lsb3p, and plant FYVE proteins (SYLF) region and SH3 domain of SH3YL1 contribute to formation of a complex with Nox4-p22(phox). Interaction of p22(phox) with SH3YL1 is triggered by LPS, and the complex induces H2O2 generation and pro-inflammatory cytokine expression in mouse tubular epithelial cells. After LPS injection, SH3YL1 knockout mice show lower levels of acute kidney injury biomarkers, decreased secretion of pro-inflammatory cytokines, decreased infiltration of macrophages, and reduced tubular damage compared with wild-type (WT) mice. The results strongly suggest that SH3YL1 is involved in renal failure in LPS-induced acute kidney injury (AKI) mice. We demonstrate that formation of a ternary complex of p22(phox)-SH3YL1-Nox4, leading to H2O2 generation, induces severe renal failure in the LPS-induced AKI model. |
