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1 Nephro-Urology Unit, UCL Institute of Child Health, London, United Kingdom
2 Molecular Haematology Unit, UCL Institute of Child Health, London, United Kingdom
3 Department of Pathology & Immunology, Washington University Medical School, St. Louis, Missouri, United States
* To whom correspondence should be addressed. E-mail: p.winyard{at}ich.ucl.ac.uk.
Many molecules have been implicated in kidney development, often based on experimental animal studies with organ cultures and cell lines. There are very few studies, however, which have directly addressed equivalent living human embryonic tissues. We generated renal mesenchymal cell lines from normal human metanephroi and used a microarray strategy to define changes in gene expression after stimulation with growth factors which enhance nephrogenesis in rodents. Changes were observed in i) genes modulating diverse general cellular processes, such as matrix metalloproteinase 1 and stanniocalcin 1; ii) genes previously implicated in organogenesis e.g. sprouty 4 and midline 1; and iii) genes involved in blood vessel growth, including angiopoietin 1 and 4. Expression of these same genes was subsequently confirmed in vivo. Our novel data has identified several previously unhighlighted genes which may be implicated in differentiation programmes within early human nephrogenesis.
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