Cross talk between primary human renal tubular cells and endothelial cells in cocultures.
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.
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore.
Farah
F
Tasnim
Daniele
D
Zink
D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D018920:Coculture Techniques; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D000511:alpha-Macroglobulins / Q000378:metabolism
C066855:HGF protein, human; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000511:alpha-Macroglobulins; D017228:Hepatocyte Growth Factor