Role of integrin-linked kinase in epithelial-mesenchymal transition in crescent formation of experimental glomerulonephritis
Role of integrin-linked kinase in epithelial-mesenchymal transition in crescent formation of experimental glomerulonephritis
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DOI：
10.1093/ndt/gfl243
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发表时间：
2006-09-01
影响因子：
6.1
通讯作者：
Kagami, Shoji
中科院分区：
文献类型：
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作者：
Shimizu, Maki;Kondo, Shuji;Kagami, Shoji
背景资料。肾小球壁上皮-间充质转化(EMT)是肾小球肾炎(GN)新月体形成过程中的关键事件。整合素连接蛋白(ILK)是一种整合素胞浆结合蛋白，参与细胞黏附、细胞外基质组织和EMT的调节。转化生长因子-β(TGF-β)参与了多种组织EMT的发生和发展。为了探讨ILK是否参与肾小球新月体的形成，我们研究了Wistar京都(WKY)大鼠诱导的新月体肾炎中ILK蛋白的表达和活性。此外，我们利用培养的壁上皮细胞(PEC)观察转化生长因子-β1(TGF-β1)能否诱导肾小球EMT和ILK。在第7天，ILK在细胞新月体中被强烈诱导表达，随后在第28天纤维细胞新月体中表达减少。新月体细胞中表达ILK的细胞表达蛋白基因产物9.5(PEC标记物)、α-平滑肌肌动蛋白(α-SMA，肌成纤维细胞标记物)和转化生长因子-β1双阳性，提示ILK和转化生长因子-β1可能参与了肾小球新月体形成过程中的EMT。与新月体组织学上ILK表达的结果一致，蛋白质印迹和蛋白激酶活性检测显示ILK蛋白和活性均增加，在GN的第7天达到高峰(分别是对照的3.7倍和3.5倍)。用转化生长因子-β1诱导培养的PEC发生EMT后，ILK的表达增加到对照组的3.1倍。本研究首次为实验性肾小球肾炎细胞新月体中ILK表达和活性增加提供了证据。ILK的表达和活性增强，可能是由转化生长因子-β1引起的，与PEC诱导的EMT有关，因此可能参与了肾小球肾炎细胞新月体的形成。
Background. Glomerular parietal epithelial-mesenchymal transition (EMT) is a key event in crescent formation of glomerulonephritis (GN). Integrin-linked kinase (ILK) is an integrin cytoplasmic-binding protein that has been implicated in the regulation of cell adhesion, extracellular matrix organization and EMT. Transforming growth factor-beta (TGF-beta) is involved in the induction and progression of EMT in several tissues.Methods. To investigate whether ILK is involved in the crescent formation in GN, we studied the expression of ILK protein and activity in crescentic GN induced in Wistar Kyoto (WKY) rats. In addition, we investigated whether transforming growth factor-beta 1 (TGF-beta 1) could induce glomerular EMT and ILK by using cultured parietal epithelial cell (PEC).Results. The expression of ILK was strongly induced in cellular crescents at day 7 and followed by a decrease in fibrocellular crescents at day 28. ILK-expressing cells in cellular crescents were double-positive for protein gene product 9.5 (PEC marker), alpha-smooth muscle actin (alpha-SMA, myofibroblasts marker) and TGF-beta 1, indicating a possible contribution of ILK and TGF-beta 1 to EMT in crescent formation in GN. Consistent with the finding of histological ILK expression in crescents, western blot and kinase activity assay showed an increase in both ILK protein and activity, peaking at day 7 of GN (3.7- and 3.5-fold of control, respectively). The expression of ILK increased to 3.1-fold of control when EMT was induced in cultured PEC by TGF-beta 1.Conclusion. The present results provide the first evidence that expression and activity of ILK are increased in cellular crescents of experimental GN. Enhanced expression and activity of ILK, possibly by TGF-beta 1, is associated with the induction of EMT by PEC and thereby, may participate in the formation of cellular crescents in GN.