Trophoblast Glycoprotein: Possible Candidate Mediating Podocyte Injuries in Glomerulonephritis
Trophoblast Glycoprotein: Possible Candidate Mediating Podocyte Injuries in Glomerulonephritis
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DOI：
10.1159/000321366
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发表时间：
2010-01-01
影响因子：
4.2
通讯作者：
Doi, Toshio
中科院分区：
文献类型：
--
作者：
Murakami, Taichi;Abe, Hideharu;Doi, Toshio
背景资料：滋养层糖蛋白（Tpbg）是一种分子量为72 kDa的跨膜糖蛋白，它通过改变肌动蛋白的结构和细胞的运动性来调节上皮细胞的表型。最近，一项微阵列研究表明，Tpbg在Thy 1肾小球肾炎（Thy 1 GN）中上调。我们假设Tpbg调节细胞骨架重排和调节足细胞在病理条件下的表型改变。方法：我们检测了Tpbg在Thy 1 GN中的表达和Tpbg在小鼠足细胞中的功能。结果：Tpbg在Thy 1 GN损伤足细胞中表达上调。在体外，免疫荧光研究表明，Tpbg共定位与粘着斑蛋白，黏着斑蛋白，在平行应力纤维的形成。即使当肌动蛋白丝与细胞松弛素D解聚时，也观察到这种共定位。显性活性RhoA诱导Tpbg在粘连灶的定位，并通过ROCK 1抑制剂Y-26732抑制。此外，转化生长因子-β增加Tpbg表达在局灶性粘连同时重排的应力纤维。应力纤维的形成被抑制在分化的足细胞转染全长Tpbg。此外，敲低Tpbg使用小干扰RNA减少足细胞的运动。结论：我们的研究结果表明，Tpbg在受损足细胞的表型改变的新作用，我们因此提出了一个新的肾小球肾炎肾小球损伤的机制。版权所有（C）2010 S. Karger AG，巴塞尔
Background: Trophoblast glycoprotein (Tpbg), a 72-kDa transrnembrane glycoprotein, is known to regulate the phenotypes of epithelial cells by modifying actin organization and cell motility. Recently, a microarray study showed that Tpbg is upregulated in Thy1 glomerulonephritis (Thy1 GN). We hypothesized that Tpbg regulates cytoskeletal rearrangement and modulates phenotypic alteration in podocytes under pathological conditions. Methods: We examined Tpbg expression in Thy1 GN and Tpbg function in mouse podocytes. Results: We demonstrated that Tpbg is upregulated in the injured podocytes of Thy1 GN. In vitro, immunofluorescence studies revealed that Tpbg colocalized with the focal adhesion protein, vinculin, in parallel with stress fiber formation. This colocalization was observed even when actin filaments were depolymerized with cytochalasin D. Tpbg localization at focal adhesions was induced by dominant-active RhoA and suppressed by the ROCK1 inhibitor Y-26732. In addition, transforming growth factor-beta increased Tpbg expression at focal adhesions concurrently with rearrangement of stress fibers. Stress fiber formation was suppressed in differentiated podocytes transfected with full-length Tpbg. Furthermore, knockdown of Tpbg using small interfering RNA decreased podocyte motility. Conclusion: Our findings suggest a novel role of Tpbg in the phenotypic alteration of injured podocytes, and we accordingly propose a new mechanism of glomerular injury in glomerulonephritis. Copyright (C) 2010 S. Karger AG, Basel