Center for Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, PR China.
Center for Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, PR China.
Cell Signal. 2018 Jan;42:249-258. doi: 10.1016/j.cellsig.2017.10.014. Epub 2017 Nov 12.
The CD38, possessing ADP-ribosyl cyclase (ADPR-cyclase) and cyclic ADP-ribose hydrolase (cADPR-hydrolase), is able to regulate a variety of cellular activities. However, the role and mechanisms for CD38 in macrophage activation and sepsis-induced acute kidney injury (AKI) remain to be determined. Here we report that in cultured macrophages, Lipopolysaccharide (LPS) could upregulate CD38 expression in time and dose dependent manner. Knocking down or blockade of CD38 in macrophages could inhibit LPS-induced macrophage M1 polarization accompanied by diminished NF-κB signaling activation. In mouse model with LPS-induced acute kidney injury, blocking CD38 with quercetin could significantly relieve kidney dysfunction, kidney pathological changes as well as inflammatory cell accumulation. Similar to those in the cultured cells, quercetin could inhibit macrophage M1 polarization and NF-κB signaling activation in macrophages from kidneys and spleens in mice after LPS injection. Together, these results demonstrate that CD38 mediates LPS-induced macrophage activation and AKI, which may be treated as a therapeutic target for sepsis-induced AKI in patients.
CD38 具有 ADP-核糖基环化酶 (ADPR-cyclase) 和环 ADP-核糖水解酶 (cADPR-hydrolase) 活性，能够调节多种细胞活动。然而，CD38 在巨噬细胞激活和脂多糖 (LPS) 诱导的急性肾损伤 (AKI) 中的作用和机制仍有待确定。在这里，我们报告在培养的巨噬细胞中，LPS 可以时间和剂量依赖性地上调 CD38 的表达。敲低或阻断巨噬细胞中的 CD38 可以抑制 LPS 诱导的巨噬细胞 M1 极化，同时 NF-κB 信号激活减弱。在 LPS 诱导的急性肾损伤的小鼠模型中，用槲皮素阻断 CD38 可显著缓解肾功能障碍、肾脏病理变化和炎性细胞积聚。与在培养细胞中一样，槲皮素可抑制 LPS 注射后肾脏和脾脏巨噬细胞中 M1 极化和 NF-κB 信号激活。综上所述，这些结果表明 CD38 介导 LPS 诱导的巨噬细胞激活和 AKI，这可能是治疗 LPS 诱导的 AKI 的一个潜在靶点。
