CYTOKINE, CHEMOKINE AND GROWTH-FACTOR EXPRESSION IN THE PATHOGENESIS OF PROGRESSIVE RENAL DAMAGE

Chronic renal diseases are untreatable conditions characterized by a f inal phase of progressive impairment of renal function, leading to end -stage renal failure (ESRF). Once the primary injury has damaged a par t of the nephron, the remainder undergo a number of adaptative changes leading to glomerulosclerosis, interstitial fibrosis and, consequentl y, end-stage kidney disease. Glomerular lesions, mainly represented by mesangial cell proliferation, mononuclear cell infiltration and extra cellular matrix deposition, have always been considered as the key fac tors in the progression of renal damage. However, in this context, it is now clear that the degree of tubulointerstitial damage is a better prognostic marker than the extent of glomerular lesions. Tubulointerst itial involvement is characterized by monocyte and neutrophil infiltra tion, tubular atrophy, proliferation of interstitial fibroblasts, that acquire a myofibroblast-like phenotype and, finally, extracellular ma trix deposition. The pathogenesis of these histological changes is lar gely unknown, but there is an increasing body of evidence suggesting t he possible involvement of some soluble factors produced and released locally, such as cytokines, chemokines and growth factors. Aiming to e lucidate the pathogenetic mechanisms underlying glomerular and tubuloi nterstitial damage in progressive renal diseases, we investigated the renal gene and protein expression of some of these soluble factors. On the basis of the histopathological lesions, we decided to focus our a ttention on monocyte chemotactic peptide-1 (MCP-1), a specific chemota ctic and activating factor for monocytes, on complement C3, a powerful activator of neutrophils, on epidermal growth factor (EGF), the physi ological modulator of tubular cell growth, on platelet-derived growth factor (PDGF), the most powerful mitogenic and activating peptide for mesenchymal cells and on transforming growth factor-beta (TGF-beta), t he main regulator of extracellular matrix synthesis and degradation.