期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 22, 期 9, 页码 4550-4554出版社
WILEY
DOI: 10.1111/jcmm.13736
关键词
ANCA; Rho GTPases; sphingosine-1-phosphate; vasculitis
资金
- National Key Research and Development Program [2016YFC0906102]
- National Natural Science [81425008, 81621092]
- Peking University Health Science Center [BMU2017CJ002]
- University of Michigan Health System
- Peking University Health Sciences Center Joint Institute for Translational and Clinical Research [BMU2017JI005]
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.
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