Dual involvement of growth arrest-specific gene 6 in the early phase of human IgA nephropathy.
Dual involvement of growth arrest-specific gene 6 in the early phase of human IgA nephropathy.
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DOI：
10.1371/journal.pone.0066759
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Doi T
中科院分区：
文献类型：
--
作者：
Nagai K;Miyoshi M;Kake T;Fukushima N;Matsuura M;Shibata E;Yamada S;Yoshikawa K;Kanayama HO;Fukawa T;Yamaguchi K;Izaki H;Mima A;Abe N;Araoka T;Murakami T;Kishi F;Kishi S;Tominaga T;Moriya T;Abe H;Doi T
Gas 6是一种生长因子，在肾小球肾炎的发展中引起系膜细胞增殖。Gas 6可与Axl、Dtk和Mer三种受体结合。然而，它们在不同类型肾小球细胞中的表达和功能尚不完全清楚。同时，代表性的细胞周期调节蛋白p27已被报道在正常肾小球的足细胞中表达，而在增殖肾小球中表达降低，其与人伊加肾病（IgAN）的系膜增殖呈负相关。本研究的目的是阐明Gas 6参与IgAN的进展。对31例经活检证实的IgA肾病患者进行了Gas 6/Axl/Dtk的检测。我们将表达水平与组织学严重程度或临床数据进行比较。此外，我们研究了Gas 6及其受体在培养足细胞中的表达。31例中有28例Gas 6主要在足细胞中表达上调。另外3例Gas 6在内皮细胞和系膜细胞中表达，与动物肾炎模型相似。在28例足细胞型肾小球肾炎中，Gas 6的表达水平与IgAN Oxford分型肾小球系膜细胞增生评分及尿蛋白排泄量相关。肾小球中p27表达也呈负相关。Axl主要表达于内皮细胞和系膜细胞，Dtk主要表达于足细胞。体外培养的小鼠足细胞表达Dtk，Gas 6刺激可降低p27的表达。Gas 6在IgAN的内皮/系膜细胞或足细胞中唯一上调。该表达模式可作为IgAN分类的标志物。Gas 6不仅可能通过Axl参与肾小球系膜增殖，而且可能通过Dtk参与IgAN足细胞损伤。
Gas6 is a growth factor that causes proliferation of mesangial cells in the development of glomerulonephritis. Gas6 can bind to three kinds of receptors; Axl, Dtk, and Mer. However, their expression and functions are not entirely clear in the different glomerular cell types. Meanwhile, representative cell cycle regulatory protein p27 has been reported to be expressed in podocytes in normal glomeruli with decreased expression in proliferating glomeruli, which inversely correlated with mesangial proliferation in human IgA nephropathy (IgAN). The aim of this study is to clarify Gas6 involvement in the progression of IgAN. Expression of Gas6/Axl/Dtk was examined in 31 biopsy proven IgAN cases. We compared the expression levels with histological severity or clinical data. Moreover, we investigated the expression of Gas6 and its receptors in cultured podocytes. In 28 of 31 cases, Gas6 was upregulated mainly in podocytes. In the other 3 cases, Gas6 expression was induced in endothelial and mesangial cells, which was similar to animal nephritis models. Among 28 podocyte type cases, the expression level of Gas6 correlated with the mesangial hypercellularity score of IgAN Oxford classification and urine protein excretion. It also inversely correlated with p27 expression in glomeruli. As for the receptors, Axl was mainly expressed in endothelial and mesangial cells, while Dtk was expressed in podocytes. In vitro, Dtk was expressed in cultured murine podocytes, and the expression of p27 was decreased by Gas6 stimulation. Gas6 was uniquely upregulated in either endothelial/mesangial cells or podocytes in IgAN. The expression pattern can be used as a marker to classify IgAN. Gas6 has a possibility to be involved in not only mesangial proliferation via Axl, but also podocyte injury via Dtk in IgAN.
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影响因子：
3.7
作者：
Ebefors K;Granqvist A;Ingelsten M;Mölne J;Haraldsson B;Nyström J
通讯作者：
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影响因子：
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影响因子：
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