Abstract：
Galactose-deficient immunoglobulin A1 (Gd-IgA1) plays a crucial role in the development of IgA nephropathy (IgAN). However, the pathological role of Gd-IgA1-containing immune complexes (ICs) and the mechanism of deposition in the mesangial region remain unclear.
To examine the deposition of Gd-IgA1-containing ICs in the mesangial region through glomerular endothelial cell injury, we evaluated the alteration of renal microvascular endothelial glycocalyx in nude mice injected with Gd-IgA1-IgG ICs. Human renal glomerular endothelial cells (HRGECs) were used to assess the potential capacity of Gd-IgA1-IgG ICs to activate endothelial cells.
Nude mice injected with Gd-IgA1-containing ICs showed podocyte and endothelial cell injuries, with IgA, IgG and C3 depositions in glomerular capillaries and the mesangium. Moreover, albuminuria and hematuria were induced. Real-time glycocalyx imaging showed that renal microvascular glycocalyx was decreased immediately after injection of Gd-IgA1-containing ICs and then mesangial IgA deposition was increased. After coculture of Gd-IgA1-containing ICs with HRGECs, messenger RNA expression levels of endothelial adhesion molecules and proinflammatory mediators were upregulated significantly.
Gd-IgA1-IgG ICs had a high affinity for glomerular endothelial cells, which resulted in glomerular filtration barrier dysfunction mediated by glycocalyx loss. Furthermore, Gd-IgA1-IgG ICs accelerated the production of adhesion factors and proinflammatory cytokines in glomerular endothelial cells. The glomerular endothelial cell injury induced by Gd-IgA1-containing ICs may enhance the permeability of Igs in the mesangial region and subsequent inflammatory responses in the pathogenesis of IgAN.
To examine the deposition of Gd-IgA1-containing ICs in the mesangial region through glomerular endothelial cell injury, we evaluated the alteration of renal microvascular endothelial glycocalyx in nude mice injected with Gd-IgA1-IgG ICs. Human renal glomerular endothelial cells (HRGECs) were used to assess the potential capacity of Gd-IgA1-IgG ICs to activate endothelial cells.
Nude mice injected with Gd-IgA1-containing ICs showed podocyte and endothelial cell injuries, with IgA, IgG and C3 depositions in glomerular capillaries and the mesangium. Moreover, albuminuria and hematuria were induced. Real-time glycocalyx imaging showed that renal microvascular glycocalyx was decreased immediately after injection of Gd-IgA1-containing ICs and then mesangial IgA deposition was increased. After coculture of Gd-IgA1-containing ICs with HRGECs, messenger RNA expression levels of endothelial adhesion molecules and proinflammatory mediators were upregulated significantly.
Gd-IgA1-IgG ICs had a high affinity for glomerular endothelial cells, which resulted in glomerular filtration barrier dysfunction mediated by glycocalyx loss. Furthermore, Gd-IgA1-IgG ICs accelerated the production of adhesion factors and proinflammatory cytokines in glomerular endothelial cells. The glomerular endothelial cell injury induced by Gd-IgA1-containing ICs may enhance the permeability of Igs in the mesangial region and subsequent inflammatory responses in the pathogenesis of IgAN.
摘要：
半乳糖缺陷型免疫球蛋白A1(Gd-IgA1)在IgA肾病(IgAN)的发生发展中起着至关重要的作用。然而,含Gd-IgA1的免疫复合物(IC)的病理作用和在肾小球系膜区域的沉积机制尚不清楚.
为了通过肾小球内皮细胞损伤检查肾小球系膜区域含有Gd-IgA1的IC的沉积，我们评估了注射Gd-IgA1-IgGIC的裸鼠肾脏微血管内皮糖萼的变化。人肾小球内皮细胞（HRGEC）用于评估Gd-IgA1-IgGIC激活内皮细胞的潜在能力。
注射含有Gd-IgA1的IC的裸鼠显示足细胞和内皮细胞损伤，IgA,IgG和C3在肾小球毛细血管和系膜中沉积。此外，引起蛋白尿和血尿。实时糖萼成像显示，注射含Gd-IgA1的IC后，肾脏微血管糖萼立即减少，然后肾小球系膜IgA沉积增加。含Gd-IgA1的IC与HRGEC共培养后，内皮粘附分子和促炎介质的信使RNA表达水平显著上调。
Gd-IgA1-IgGIC对肾小球内皮细胞有很高的亲和力，这导致由糖萼丢失介导的肾小球滤过屏障功能障碍。此外，Gd-IgA1-IgGIC加速了肾小球内皮细胞中粘附因子和促炎细胞因子的产生。含有Gd-IgA1的IC诱导的肾小球内皮细胞损伤可能会增强IgAN发病机理中肾小球系膜区域Igs的通透性和随后的炎症反应。
为了通过肾小球内皮细胞损伤检查肾小球系膜区域含有Gd-IgA1的IC的沉积，我们评估了注射Gd-IgA1-IgGIC的裸鼠肾脏微血管内皮糖萼的变化。人肾小球内皮细胞（HRGEC）用于评估Gd-IgA1-IgGIC激活内皮细胞的潜在能力。
注射含有Gd-IgA1的IC的裸鼠显示足细胞和内皮细胞损伤，IgA,IgG和C3在肾小球毛细血管和系膜中沉积。此外，引起蛋白尿和血尿。实时糖萼成像显示，注射含Gd-IgA1的IC后，肾脏微血管糖萼立即减少，然后肾小球系膜IgA沉积增加。含Gd-IgA1的IC与HRGEC共培养后，内皮粘附分子和促炎介质的信使RNA表达水平显著上调。
Gd-IgA1-IgGIC对肾小球内皮细胞有很高的亲和力，这导致由糖萼丢失介导的肾小球滤过屏障功能障碍。此外，Gd-IgA1-IgGIC加速了肾小球内皮细胞中粘附因子和促炎细胞因子的产生。含有Gd-IgA1的IC诱导的肾小球内皮细胞损伤可能会增强IgAN发病机理中肾小球系膜区域Igs的通透性和随后的炎症反应。
