Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore.
Am J Physiol Renal Physiol. 2012 Apr 15;302(8):F1055-62. doi: 10.1152/ajprenal.00621.2011. Epub 2012 Feb 8.
Interactions between renal tubular epithelial cells and adjacent endothelial cells are essential for normal renal functions but also play important roles in renal disease and repair. Here, we investigated cocultures of human primary renal proximal tubular cells (HPTC) and human primary endothelial cells to address the cross talk between these cell types. HPTC showed improved proliferation, marker gene expression, and enzyme activity in cocultures. Also, the long-term maintenance of epithelia formed by HPTC was improved, which was due to the secretion of transforming growth factor-β1 and its antagonist α2-macroglobulin. HPTC induced endothelial cells to secrete increased amounts of these factors, which balanced each other functionally and only displayed in combination the observed positive effects. In addition, in the presence of HPTC endothelial cells expressed increased amounts of hepatocyte growth factor and vascular endothelial growth factor, which have well-characterized effects on renal tubular epithelial cells as well as on endothelial cells. Together, the results showed that HPTC stimulated endothelial cells to express a functionally balanced combination of various factors, which in turn improved the performance of HPTC. The results give new insights into the cross talk between renal epithelial and endothelial cells and suggest that cocultures could be also useful models for the analysis of cellular communication in renal disease and repair. Furthermore, the characterization of defined microenvironments, which positively affect HPTC, will be helpful for improving the performance of this cell type in in vitro applications including in vitro toxicology and kidney tissue engineering.
肾小管上皮细胞与相邻内皮细胞之间的相互作用对于正常的肾功能至关重要，但它们在肾脏疾病和修复中也发挥着重要作用。在这里，我们研究了人原代近端肾小管细胞 (HPTC) 和人原代内皮细胞的共培养物，以探讨这两种细胞类型之间的串扰。HPTC 在共培养物中表现出增殖、标记基因表达和酶活性的提高。此外，HPTC 形成的上皮细胞的长期维持也得到了改善，这归因于转化生长因子-β1 及其拮抗剂 α2-巨球蛋白的分泌。HPTC 诱导内皮细胞分泌更多数量的这些因子，它们在功能上相互平衡，只有在组合时才会显示出观察到的积极效果。此外，在 HPTC 的存在下，内皮细胞表达了更多的肝细胞生长因子和血管内皮生长因子，这些因子对肾小管上皮细胞和内皮细胞都有很好的作用。总之，这些结果表明，HPTC 刺激内皮细胞表达具有功能平衡的多种因子的组合，这反过来又改善了 HPTC 的性能。这些结果为肾脏上皮细胞和内皮细胞之间的串扰提供了新的见解，并表明共培养物也可以作为分析肾脏疾病和修复中细胞通讯的有用模型。此外，对能积极影响 HPTC 的特定微环境的表征将有助于改善该细胞类型在体外应用中的性能，包括体外毒理学和肾脏组织工程。
