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Title: FGF2 requirement for podocyte maturation in-vitro
Author: Davidson, Gary
ISNI:       0000 0001 3407 812X
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2000
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FGF2 is expressed in renal podocytes as they differentiate in-vivo, 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 Fgf2 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 in-vivo has recently been developed. The system is based on isolation of conditionally immortalised podocyte cells derived from H-2KbtsA58 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 in-vivo, 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 Slug 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. Fgf7 and Fgf10 expressions are lost in Fgf2 deficient MPC cells, but not in Fgf2 deficient kidney cortex, affording an explanation to the emergence of a stronger defect in-vitro.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Renal; Glomeruli; Kidney; Growth factor