Dept. of Pediatrics, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave., Madison, WI 53792-4108, USA.
Am J Physiol Renal Physiol. 2012 Apr 1;302(7):F809-19. doi: 10.1152/ajprenal.00498.2011. Epub 2011 Dec 14.
The extracellular matrix (ECM) acts as a scaffold for kidney cellular organization. Local secretion of the ECM allows kidney cells to readily adapt to changes occurring within the kidney. In addition to providing structural support for cells, the ECM also modulates cell survival, migration, proliferation, and differentiation. Although aberrant regulation of ECM proteins can play a causative role in many diseases, it is not known whether ECM production, cell adhesion, and migration are regulated in a similar manner in kidney epithelial and endothelial cells. Here, we demonstrate that lack of BIM expression differentially impacts kidney endothelial and epithelial cell ECM production, migration, and adhesion, further emphasizing the specialized role of these cell types in kidney function. Bim -/- kidney epithelial cells demonstrated decreased migration, increased adhesion, and sustained expression of osteopontin and thrombospondin-1 (TSP1). In contrast, bim -/- kidney endothelial cells demonstrated increased cell migration, and decreased expression of osteopontin and TSP1. We also observed a fivefold increase in VEGF expression in bim -/- kidney endothelial cells consistent with their increased migration and capillary morphogenesis. These cells also had decreased endothelial nitric oxide synthase activity and nitric oxide bioavailability. Thus kidney endothelial and epithelial cells make unique contributions to the regulation of their ECM composition, with specific impact on adhesive and migratory properties that are essential for their proper function.
细胞外基质 (ECM) 充当肾脏细胞组织的支架。ECM 的局部分泌使肾脏细胞能够迅速适应肾脏内发生的变化。除了为细胞提供结构支持外,ECM 还调节细胞存活、迁移、增殖和分化。尽管 ECM 蛋白的异常调节可能在许多疾病中起因果作用,但尚不清楚 ECM 产生、细胞黏附和迁移是否以类似的方式在肾脏上皮细胞和内皮细胞中受到调节。在这里,我们证明 BIM 表达的缺失会以不同的方式影响肾脏内皮细胞和上皮细胞 ECM 的产生、迁移和黏附,这进一步强调了这些细胞类型在肾脏功能中的特殊作用。Bim -/- 肾脏上皮细胞表现出迁移减少、黏附增加以及骨桥蛋白和血小板反应蛋白-1 (TSP1) 的持续表达。相比之下,Bim -/- 肾脏内皮细胞表现出细胞迁移增加,以及骨桥蛋白和 TSP1 的表达减少。我们还观察到 Bim -/- 肾脏内皮细胞中 VEGF 的表达增加了五倍,这与它们的迁移增加和毛细血管形态发生一致。这些细胞还表现出内皮型一氧化氮合酶活性和一氧化氮生物利用度降低。因此,肾脏内皮细胞和上皮细胞对 ECM 组成的调节做出了独特的贡献,对其黏附性和迁移性有特定的影响,这对其正常功能至关重要。