FGF2 is expressed in renal podocytes as they differentiate <I>in-vivo</I>, as demonstrated by specific antibody staining within developing glomeruli of chicken metanephros. Mice lacking FGF2 have been generated in the laboratory by targeted deletion and kidneys of <I>Fgf2</I> deficient mice appear to develop normally. Detailed histological analysis of adult kidneys from these mice however has revealed low frequency glomerular abnormalities. Additionally, a few obvious cases of glomerulosclerosis with severe podocyte damage were observed specifically in mutant mice. Taken together these observations indicate FGF2 plays a role in podocyte development and/or function. A novel culture system that allows the induction of podocyte cell differentiation <I>in-vivo</I> has recently been developed. The system is based on isolation of conditionally immortalised podocyte cells derived from H-2K<SUP>b</SUP>tsA58 transgenic (immorto) mice. Isolation of podocyte cells from renal glomeruli of wild-type and FGF2 deficient immorto mice was performed to address the functional relevance of FGF2 in podocyte development. Conditionally immortalised wild-type podocyte cells (wild-type MPCs) display characteristic features of podocytes <I>in-vivo</I>, however Fgf2 null MPCs show striking morphological and molecular abnormalities. Mutant podocyte cells do not undergo the epithelial-to-mesenchymal transformation (EMT) associated with normal podocyte maturation and, correspondingly, fail to differentiate. The EMT mediator <I>Slug</I> is up-regulated as wild-type cells differentiate but is missing in mutant cells, suggesting this transcription factor acts downstream of FGF signalling to mediate EMT associate maturation of podocytes. <I>Fgf7</I> and <I>Fgf10</I> expressions are lost in <I>Fgf2</I> deficient MPC cells, but not in <I>Fgf2</I> deficient kidney cortex, affording an explanation to the emergence of a stronger defect <I>in-vitro</I>.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:311157 |
| Date | January 2000 |
| Creators | Davidson, Gary |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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