Angiogenic protein Cyr61 is expressed by podocytes in anti-Thy-1 glomerulonephritis.
Angiogenic protein Cyr61 is expressed by podocytes in anti-Thy-1 glomerulonephritis.
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DOI：
10.1097/01.asn.0000060576.61218.3d
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发表时间：
2003-05
期刊：
影响因子：
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通讯作者：
K. Sawai;K. Mori;M. Mukoyama;A. Sugawara;T. Suganami;M. Koshikawa;K. Yahata;H. Makino;T. Nagae;Y. Fujinaga;H. Yokoi;T. Yoshioka;A. Yoshimoto;I. Tanaka;K. Nakao
中科院分区：
文献类型：
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作者：
K. Sawai;K. Mori;M. Mukoyama;A. Sugawara;T. Suganami;M. Koshikawa;K. Yahata;H. Makino;T. Nagae;Y. Fujinaga;H. Yokoi;T. Yoshioka;A. Yoshimoto;I. Tanaka;K. Nakao
抗Thy-1肾小球肾炎（anti-Thy-1GN）肾小球结构严重损伤后可动态恢复，但其机制尚待进一步研究。为了鉴定可能参与肾小球重建的候选基因，筛选由足细胞特异性表达并且在Thy-1 GN的肾小球中上调的基因。其中，富含半胱氨酸的蛋白61（Cyr 61或CCN 1），属于CCN家族的可溶性血管生成蛋白，被鉴定。通过北方印迹分析，Cyr 61 mRNA在Thy-1 GN的肾小球中从第3天至第7天显著上调，此时系膜细胞迁移最为显著。原位杂交和免疫组化结果显示，Cyr 61 mRNA和蛋白在正常大鼠肾近端直小管、输入小动脉和输出小动脉中均有表达，在Thy-1 GN足细胞中表达明显上调。血小板源性生长因子-BB（PDGF-BB）和转化生长因子-β 1（TGF-β 1），其中的基因表达在肾小球的Thy-1 GN的上调在类似的时间过程中作为Cyr 61，诱导Cyr 61 mRNA表达在培养的足细胞。此外，Cyr 61过表达细胞的上清液抑制PDGF诱导的系膜细胞迁移。总之，表明Cyr 61在Thy-1 GN中的足细胞处可能通过PDGF和TGF-β强烈上调。Cyr 61可能作为足细胞分泌的抑制系膜细胞迁移的因子参与肾小球重塑。
Dynamic recovery of glomerular structure occurs after severe glomerular damage in anti-Thy-1 glomerulonephritis (Thy-1 GN), but its mechanism remains to be investigated. To identify candidate genes possibly involved in glomerular reconstruction, screening was performed for genes that are specifically expressed by podocytes and are upregulated in glomeruli of Thy-1 GN. Among them, cysteine-rich protein 61 (Cyr61 or CCN1), a soluble angiogenic protein belonging to the CCN family, was identified. By Northern blot analysis, Cyr61 mRNA was markedly upregulated in glomeruli of Thy-1 GN from day 3 through day 7, when mesangial cell migration was most prominent. By in situ hybridization and immunohistochemistry, Cyr61 mRNA and protein were expressed by proximal straight tubules and afferent and efferent arterioles in normal rat kidneys and were intensely upregulated at podocytes in Thy-1 GN. Platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-beta1 (TGF-beta1), of which the gene expression in the glomeruli of Thy-1 GN was upregulated in similar time course as Cyr61, induced Cyr61 mRNA expression in cultured podocytes. Furthermore, supernatant of Cyr61-overexpressing cells inhibited PDGF-induced mesangial cell migration. In conclusion, it is shown that Cyr61 is strongly upregulated at podocytes in Thy-1 GN possibly by PDGF and TGF-beta. Cyr61 may be involved in glomerular remodeling as a factor secreted from podocytes to inhibit mesangial cell migration.