No abstract

Background: Renal arteriolar microangiopathic (MA) lesions were common in IgA nephropathy (IgAN) and their presence was an independent risk factor for kidney failure. Endothelial injury is regarded as the most important cause of MA lesions. The deposition of circulating IgA1 complex (cIgA1) in the glomerular mesangium has been regarded as the most important mechanism to induce the injury of podocyte and tubular epithelium. Whether cIgA1 can induce vascular endothelial injury is not clear.Methods: Blood of 59 IgAN patients and 19 healthy controls was collected, pending the measurement of Willebrand factor (vWF) and soluble vascular cell adhesion molecule 1 (sVCAM1) and Heparin-binding EGF-like growth factor (HB-EGF) by ELISA. cIgA1 was isolated from 12 primary IgAN patients who had not been treated with steroids or immunosuppressants and 10 healthy controls. Then, IgA-HMC medium (IgA-HMCM) was prepared by collecting the cell culture supernatants of growth-arrested HMCs grown in medium containing cIgA1. Human umbilical vein endothelial cells (HUVECs) were cultured with the IgA-HMCM in the presence or absence of Panax notoginseng saponins (PNS), which are anti-inflammatory bioactive components of the Chinese medicinal herb Panax notoginseng. The protein levels of interleukin-6 (IL-6) and chemokine (C-X-C motif) ligand 1 (CXCL1) in IgA-HMCM and vWF, sVCAM1 and HB-EGF in HUVEC medium were determined by ELISA. Results: IgAN patients had higher levels of vWF, sVCAM-1 and HB-EGF than that in healthy controls. cIgA1 from IgAN patients (IgAN-cIgA1) induced significantly higher expression levels of IL-6 and CXCL1 in HMCM than cIgA1 from healthy controls. vWF, sVCAM1 and HB-EGF levels induced by conditioned IgAN-cIgA1-treated HMCM (IgAN-HMCM) were significantly higher than the levels induced by conditioned cIgA1-treated HMCM from healthy controls (HC-HMCM). After HUVECs were cultured in PNS and IgAN-HMCM, the levels of vWF, sVCAM1 and HB-EGF were significantly lower in the culture supernatants of cells cultured in PNS and IgAN-HMCM than in that of cells cultured in IgAN-HMCM alone. Conclusion: cIgA1 could activate mesangial cells and, in turn, induce the injury of endothelial cells by inflammation factors in vitro.