Plasma Gelsolin Promotes Proliferation of Mesangial Cell in IgA Nephropathy
Plasma Gelsolin Promotes Proliferation of Mesangial Cell in IgA Nephropathy
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血浆凝溶胶蛋白促进 IgA 肾病系膜细胞增殖
DOI：
10.1159/000453199
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发表时间：
2016-12
影响因子：
--
通讯作者：
Xiaoming Jin
中科院分区：
文献类型：
--
作者：
Lei Zhang;Dan Kong;Hongxue Meng;Changsong Han;Jiang Zhu;Juanjuan Qiao;Yan He;Tianzhen Wang;Xiaobo Li;Fengmin Zhang;Xiaoming Jin
背景/目的：血浆凝溶胶蛋白（pGSN）是一种肌动蛋白结合蛋白，在类风湿性关节炎的发病机制中发挥着关键作用。然而，pGSN是否参与其他免疫性疾病仍不清楚。本研究旨在探讨pGSN与伊加肾病（IgAN）的关系。研究方法：200名IgAN患者，200名其他类型肾病患者和2000年至2014年期间接受肾活检的健康对照（HC）患者参加了这项研究。牛津分类系统用于预测疾病进展的风险。检测血清及肾组织中pGSN，分析pGSN与伊加、半乳糖缺陷型IgA 1（Gd-IgA 1）、转化生长因子β 1（TGF-β1）、纤维连接蛋白（FN）含量、临床症状及肾功能的相关性。结果如下：我们发现IgAN患者血清中的pGSN水平与其他形式的肾小球肾炎和HC患者血清相比显著降低。血清pGSN水平与IgA 1、FN、TGF-β1水平呈负相关，与肾小球滤过率呈正相关。IgAN患者肾小球pGSN含量显著升高，并与TGF-β1和FN水平呈正相关。在肾组织中，M1和S1型IgAN患者的pGSN水平显著高于M0和S 0型患者（p < 0.05）。同时，pGSN通过促进细胞有丝分裂促进人肾小球系膜细胞（HMC）增殖。pGSN还可促进HMC中整合素α2β1的表达，并增强整合素α2β1与pGSN的相互作用。结论：提示pGSN可能通过促进系膜细胞增殖在IgAN的发生发展中起重要作用，血清和肾小球pGSN水平可能是预测IgAN进展和预后的新指标。
Background/Aims: Plasma gelsolin (pGSN) is an actin-binding protein that plays a critical role in the pathogenesis of rheumatoid arthritis. However, whether pGSN is involved in other immunological diseases remains unknown. This study focused on the relationship between pGSN and immunoglobulin A (IgA) nephropathy (IgAN). Methods: Two hundred patients with IgAN, 200 patients each with several other types of nephropathy and healthy controls (HCs) who underwent kidney biopsies between 2000 and 2014 were enrolled in the study. The Oxford classification system was used to predict the risk of disease progression. Serum and renal tissue were used to detect pGSN, and the correlations between pGSN and IgA, galactose-deficient IgA1 (Gd-IgA1), transforming growth factor beta1 (TGF-β1), fibronectin (FN) content, clinical symptoms, and kidney function were analyzed. Results: We found that the pGSN levels were significantly decreased in sera from IgAN patients compared to sera from patients with other forms of glomerular nephritis and HCs. Furthermore, the serum pGSN levels were negatively correlated with the serum IgA1, FN, and TGF-β1 levels, and positively correlated with the estimated glomerular filtration rate. Conversely, the glomerular pGSN content was significantly elevated in the IgAN patients and was positively correlated with TGF-β1 and FN levels. In renal tissue, the pGSN levels were significantly higher in IgAN patients with M1 and S1 compared to patients with M0 and S0 (p < 0.05). Meanwhile, pGSN promoted human mesangial cell (HMC) proliferation by facilitating cell mitosis in vitro. pGSN also promoted integrin α2β1 expression in HMCs and enhanced the integrin α2β1-pGSN interaction. Conclusion: Our study suggested that pGSN may play an important role in the development of IgAN by promoting the proliferation of mesangial cells and that serum and glomerular pGSN levels may be new markers for predicting IgAN progression and prognosis.
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影响因子：
4.9
作者：
Osborn, Teresia M.;Verdrengh, Margareta;Stossel, Thomas P.;Tarkowski, Andrej;Bokarewa, Maria
通讯作者：
Bokarewa, Maria
影响因子：
4.6
作者：
Y. Wang;M. Zhao;Y.‐K. Zhang;X. Li;H-y Wang
通讯作者：
Y. Wang;M. Zhao;Y.‐K. Zhang;X. Li;H-y Wang
影响因子：
3.2
作者：
Liu, Xiujuan;Hong, Quan;Xu, Lihong
通讯作者：
Xu, Lihong
影响因子：
3.3
作者：
J. Wada;H. Sugiyama;H. Makino
通讯作者：
J. Wada;H. Sugiyama;H. Makino
影响因子：
3.7
作者：
Marrocco, Cristina;Rinalducci, Sara;Zolla, Lello
通讯作者：
Zolla, Lello