Yuan Yi, Yang Mingyue, Wang Kuo, Sun Jing, Song Lili, Diao Xue, Jiang Zhenyu, Cheng Genhong, Wang Xiaosong
Institute of Translational Medicine, the First Hospital, Jilin University, Changchun, 130061, China.
Department of Rheumatology and Immunology, the First Hospital, Jilin University, Changchun, 130021, China.
Arthritis Res Ther. 2017 Mar 29;19(1):70. doi: 10.1186/s13075-017-1238-8.
Our aim is to study the existence of the TLR9/TGF-β1/PDGF-B pathway in healthy humans and patients with systemic lupus erythematosus (SLE), and to explore its possible involvement in the pathogenesis of lupus nephritis (LN).
Protein levels of the cytokines were detected by ELISA. mRNA levels of the cytokines were analyzed by real-time PCR. MTT assay was used to test the proliferation of mesangial cells under different treatments.
Compared to healthy controls (N = 56), levels of Toll-like receptor (TLR)9, transforming growth factor (TGF)-β1, and platelet-derived growth factor B (PDGF-B) were increased significantly in the peripheral blood of SLE patients (N = 112). Significant correlations between the levels of TLR9, TGF-β1, and PDGF-B were observed in both healthy controls and SLE patients. The levels of TGF-β1 and PDGF-B were greatly enhanced by TLR9 activation in primary cell cultures. The proliferation of mesangial cells induced by the plasma of SLE patients was significantly higher than that induced by healthy controls; PDGF-B was involved in this process. The protein levels of PDGF-B homodimer correlated with the levels of urine protein in SLE patients with LN (N =38).
The TLR9/TGF-β1/PDGF-B pathway exists in humans and can be excessively activated in SLE patients. High levels of PDGF-B may result in overproliferation of mesangial cells in the kidney that are involved in the development of glomerulonephritis and LN. Further studies are necessary to identify TLR9, TGF-β1, and PDGF-B as new therapeutic targets to prevent the development of glomerulonephritis and LN.
我们的目的是研究Toll样受体9（TLR9）/转化生长因子β1（TGF-β1）/血小板衍生生长因子B（PDGF-B）通路在健康人和系统性红斑狼疮（SLE）患者中的存在情况，并探讨其可能参与狼疮性肾炎（LN）发病机制的作用。
采用酶联免疫吸附测定（ELISA）检测细胞因子的蛋白水平。通过实时聚合酶链反应（PCR）分析细胞因子的信使核糖核酸（mRNA）水平。采用MTT法检测不同处理条件下系膜细胞的增殖情况。
与健康对照者（n = 56）相比，SLE患者（n = 112）外周血中Toll样受体（TLR）9、转化生长因子（TGF）-β1和血小板衍生生长因子B（PDGF-B）水平显著升高。在健康对照者和SLE患者中均观察到TLR9、TGF-β1和PDGF-B水平之间存在显著相关性。在原代细胞培养中，TLR9激活可显著提高TGF-β1和PDGF-B水平。SLE患者血浆诱导的系膜细胞增殖显著高于健康对照者；PDGF-B参与了这一过程。LN的SLE患者（n = 38）中，PDGF-B同型二聚体的蛋白水平与尿蛋白水平相关。
TLR9/TGF-β1/PDGF-B通路存在于人体中，且在SLE患者中可过度激活。高水平的PDGF-B可能导致肾脏系膜细胞过度增殖，参与肾小球肾炎和LN的发生发展。有必要进一步研究将TLR9、TGF-β1和PDGF-B确定为预防肾小球肾炎和LN发生发展的新治疗靶点。
