Department of Nephrology, Graduate School of Medicine, Institute of Health-Bio-Science, University of Tokushima, Tokushima University Hospital, Tokushima, Japan.
Am J Nephrol. 2010;32(6):505-21. doi: 10.1159/000321366. Epub 2010 Oct 27.
trophoblast glycoprotein (Tpbg), a 72-kDa transmembrane 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.
we examined Tpbg expression in Thy1 GN and Tpbg function in mouse podocytes.
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-β 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.
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.
滋养层糖蛋白（Tpbg）是一种 72kDa 的跨膜糖蛋白，已知通过调节肌动蛋白组织和细胞运动来调节上皮细胞的表型。最近，一项微阵列研究表明 Tpbg 在 Thy1 肾小球肾炎（Thy1 GN）中上调。我们假设 Tpbg 调节细胞骨架重排，并在病理条件下调节足细胞的表型改变。
我们检查了 Thy1 GN 中的 Tpbg 表达和小鼠足细胞中的 Tpbg 功能。
我们证明 Tpbg 在 Thy1 GN 的损伤足细胞中上调。在体外，免疫荧光研究显示 Tpbg 与粘着斑蛋白 vinculin 共定位，与应力纤维形成平行。即使用细胞松弛素 D 使肌动蛋白丝解聚，也观察到这种共定位。Tpbg 在粘着斑处的定位是由显性活性 RhoA 诱导的，被 ROCK1 抑制剂 Y-26732 抑制。此外，转化生长因子-β（transforming growth factor-β）在应力纤维重排的同时增加粘着斑处的 Tpbg 表达。全长 Tpbg 转染的分化足细胞中应力纤维形成受到抑制。此外，用小干扰 RNA 敲低 Tpbg 会降低足细胞的迁移能力。
我们的研究结果表明 Tpbg 在损伤足细胞表型改变中的新作用，因此我们提出了肾小球肾炎中肾小球损伤的新机制。
