Diabetic nephropathy: renal development gone awry?
Nephrogenesis is controlled by a sequence of inductive signals between different areas of the developing kidney. As these signals are being elucidated, it has become clear that many important developmental genes are re-expressed in the mature organ following injury, possibly as part of repair and regeneration. While this reuse of developmental pathways may contribute to healing and repair, it may alternatively result in scar formation if specific components of the pathways are missing, if the temporal correlation of various elements is faulty, or if an injurious stimulus persists. In the review we will use diabetic nephropathy as an example to illustrate this paradigm in renal disease. The pathogenesis of diabetic nephropathy is complex and characterized by altered expression of many genes, including growth factors, apoptotic regulators, cellular matrix components, and cytoskeletal proteins. Many of these factors also function during kidney development. The elucidation of the roles these genes play in nephrogenesis and of their array of molecular partners and modulators may ultimately shed light on the pathogenesis of disease (and indeed vice versa), and may even suggest new therapeutic strategies.
Dolan
Vincent
V
Department of Medicine and Therapeutics, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, The Mater Misericordiae Hospital, Dublin, Ireland.
Hensey
Carmel
C
Brady
Hugh R
HR
D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D055513:Connective Tissue Growth Factor; D003928:Diabetic Nephropathies / Q000235:genetics*; D016228:Endothelial Growth Factors / Q000235:genetics; D004815:Epidermal Growth Factor / Q000235:genetics; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007668:Kidney / Q000196:embryology; D008222:Lymphokines / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics; D011506:Proteins / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; C526317:CCN2 protein, human; D016228:Endothelial Growth Factors; C486399:GREM1 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D011506:Proteins; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D055513:Connective Tissue Growth Factor; D004815:Epidermal Growth Factor; D020782:Matrix Metalloproteinases