Yuan M, Tan Y, Wang Y, Wang S X, Yu F, Zhao M H
1 Renal Division, Department of Medicine, Peking University First Hospital, Beijing, People's Republic of China.
2 Institute of Nephrology, Peking University, Beijing, People's Republic of China.
Lupus. 2019 Mar;28(3):347-358. doi: 10.1177/0961203319828509. Epub 2019 Feb 12.
Our study aims to evaluate the endothelial cell-podocyte crosstalk in proliferative lupus nephritis (LN). The semi-quantification scores of glomerular endothelial cell injury and the foot process width (FPW) were processed in 110 proliferative LN patients. Podocytes were stimulated with LN-derived IgG. Glomerular endothelial cells were treated with podocyte-conditioned medium (PCM), and then podocytes were incubated with endothelial cell-conditioned medium (ECM). The levels of vascular endothelial growth factor-A (VEGF-A) in PCM and endothelin-1 in ECM were analyzed, and the injury of podocyte and glomerular endothelial cells were further evaluated. The pathological score of glomerular endothelial cell injury was correlated with FPW in LN complicated with thrombotic microangiopathy. In vitro study showed the following: 1. Stimulation of podocytes by IgG from LN led to decline in the expression of nephrin with cytoskeleton rearrangement, and reduction of VEGF-A levels. 2. Exposure of glomerular endothelial cells to PCM incubated with LN-derived IgG (PCM-LN) induced more endothelin-1 secretion and disruption of intercellular tight junction. 3. Exposure of podocytes to ECM stimulated with PCM-LN could induce cytoskeleton redistribution with decrease of nephrin. In conclusion, the pathological glomerular endothelial cell lesions were associated with FPW and the VEGF-endothelin-1 system might play a critical role in the endothelial cell-podocyte crosstalk in LN.
我们的研究旨在评估增殖性狼疮性肾炎（LN）中内皮细胞与足细胞之间的相互作用。对110例增殖性LN患者的肾小球内皮细胞损伤半定量评分及足突宽度（FPW）进行了分析。用LN来源的IgG刺激足细胞。用足细胞条件培养基（PCM）处理肾小球内皮细胞，然后将足细胞与内皮细胞条件培养基（ECM）共同孵育。分析PCM中血管内皮生长因子-A（VEGF-A）水平及ECM中内皮素-1水平，并进一步评估足细胞和肾小球内皮细胞的损伤情况。在合并血栓性微血管病的LN中，肾小球内皮细胞损伤的病理评分与FPW相关。体外研究结果如下：1. LN来源的IgG刺激足细胞导致nephrin表达下降，伴有细胞骨架重排，且VEGF-A水平降低。2. 肾小球内皮细胞暴露于与LN来源的IgG共同孵育的PCM（PCM-LN）中，可诱导更多内皮素-1分泌，破坏细胞间紧密连接。3. 足细胞暴露于用PCM-LN刺激的ECM中可诱导细胞骨架重新分布，nephrin减少。总之，肾小球内皮细胞的病理损伤与FPW相关，VEGF-内皮素-1系统可能在LN的内皮细胞-足细胞相互作用中起关键作用。
