Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
Peking University Institute of Nephrology, Beijing, China.
J Cell Mol Med. 2018 Sep;22(9):4550-4554. doi: 10.1111/jcmm.13736. Epub 2018 Jul 11.
Sphingosine-1-phosphate (S1P) is a crucial regulator in vascular inflammation. Our recent study found that under pathophysiological concentration in active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), S1P participated in MPO-ANCA-positive IgG-induced glomerular endothelial cell (GEnC) activation via a S1P receptor (S1PR)-dependent way. However, the downstream signalling pathways are not fully clear yet. In this study, we demonstrated that Rho guanosine triphosphatases (GTPases) signalling pathways, RhoA and Rac1 in particular, were implicated in MPO-ANCA-positive IgG-mediated GEnCs activation enhanced by pathophysiological concentration of S1P in AAV. These results provide mechanistic insights into vascular barrier dysfunction in AAV, which may facilitate the development of effective therapies.
鞘氨醇-1-磷酸（S1P）是血管炎症的关键调节剂。我们最近的研究发现，在活性抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）的病理生理浓度下，S1P 通过 S1P 受体（S1PR）依赖性途径参与 MPO-ANCA 阳性 IgG 诱导的肾小球内皮细胞（GEnC）激活。然而，下游信号通路尚不完全清楚。在这项研究中，我们证明了Rho 鸟苷三磷酸酶（GTPases）信号通路，特别是 RhoA 和 Rac1，参与了 S1P 在 AAV 中病理生理浓度增强的 MPO-ANCA 阳性 IgG 介导的 GEnC 激活。这些结果为 AAV 中的血管屏障功能障碍提供了机制上的见解，这可能有助于开发有效的治疗方法。
