Growth factors, cytokines, and renal fibrosis during the course of diabetic nephropathy.
Diabetic nephropathy is characterised by a progressive accumulation of extracellular matrix within the glomerular mesangium and the interstitium. The pathogenesis of this fibrotic process is still poorly understood, but in vitro and in vivo data suggest that TGF-B plays a key role. Local overproduction of TGF-B could be secondary to a synthesis of diacylglycerol, polyols, or glucosamines. It may also be secondary to an accumulation of advanced glycosylation end-products which modify the functions of neighbouring cells. Moreover, clinical as well as experimental data for TGF-B suggest that angiotensin II has a profibrotic effect; and it has been clearly demonstrated that angiotensin-converting enzyme inhibitors have a beneficial effect in patients with insulin-dependent diabetes mellitus. Other molecules such as endothelin-1, lipid peroxidation products, or IGF-1 may also play a role in this fibrotic process. Finally, heavy proteinuria secondary to glomerular lesions enhances the accumulation of extracellular matrix within the interstitium, probably through modifications of tubular cell functions, thereby inducing the release of pro-inflammatory and profibrotic molecules.
Department of Nephrology, Tenon Hospital, 4 rue de la Chine, Paris, France.
J
J
Rossert
C
C
Terraz-Durasnel
G
G
Brideau
D000818:Animals; D016207:Cytokines / Q000502:physiology*; D003928:Diabetic Nephropathies / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D005355:Fibrosis; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*
D016207:Cytokines; D006133:Growth Substances