Connective Tissue Growth Factor (CTGF) and Diabetic Nephropathy (DN): Clinical marker, pathogenic factor and target for therapeutic intervention
Thursday 22 January 2009
Dr. R. Goldschmeding
Project
Transforming growth factor- Beta is considered to play a role in Diabetic Nephropathy (DN). However long term inhibition of TGF-beta ligand activity is unattractive because of the danger of hyperinflammatory responses, autoimmunity and malignanvcies. CTGF is a glucose inducible factor which is essential for effectuation of many of the pro-fibrotic actions of TGF-beta. In particular increased ECM production.
It is studied whether CTGF is an alternative target for therapy and prevention of this and other diabetic complications. Therefore we analyse the relationship betrween development and progression of DN with increased CTGF concentrations in tissue, blood and urine from humans.
Similarly, the kinetics of CTGF expression in realtion to development and progression of nephropathy is studied in urine, plasma and tissue of diabteic mice. The potential pathological relevance of CTGF activity with respect to biological changes induced by hyperglycemia is analysed in vitro (tissue culture) and in vivo (mice).
Finally it is studied (in CTGF knock-out mice) whether therapeutic (down) modulation of CTGF activity contributes to halting development , progression and or even reversal of DN.
Techniques
Immunohistochemistry, Confocal Laserscan Microscopy, Mol. Biol. Techniques such as PCR, blotting, DNA/RNA isolation, gelelectrophoresis, sequencing etc., tissue culture, ELISA, enzymography
Duration
6 or 9 months
Contact
Dr. H.F.J. Dullens, h.f.j.dullens@umcutrecht.nl, tel 088 75 565 69