Cytokines in Epithelial-Mesenchymal Transition: A New Insight Into Obstructive Nephropathy

Purpose: Tubulointerstitial fibrosis is the final common pathway to end stage renal disease. The pathophysiology of renal fibrosis involves fibroblast proliferation, macrophage infiltration, the elaboration of cytokines and other proinflammatory mediators, and an imbalance in extracellular matrix deposition and degradation. Although the exact origin of activated fibroblasts remains uncertain, emerging evidence indicates that mature tubular epithelial cells are capable of transforming into myofibroblasts under pathological conditions, a process that is called epithelial-mesenchymal transition. Materials and Methods: We reviewed the pertinent literature from January 1980 through June 2007 with regard to the contribution of epithelial-mesenchymal transition to renal fibrogenesis. Results: Epithelial-mesenchymal transition is an orchestrated, highly regulated process that proceeds in stepwise fashion and appears to contribute significantly to renal fibrosis and the progression of chronic renal disease. Several cytokines and growth factors regulate epithelial-mesenchymal transition, of which transforming growth factor-β1 is the most studied. Conclusions: Epithelial-mesenchymal transition is a cellular mechanism that has long been recognized as a central feature of normal development. However, increasing evidence implicates epithelial-mesenchymal transition in the pathophysiology of tubulointerstitial fibrosis and chronic renal disease. Recent insights into the molecular events and intrinsic signaling pathways that are active during epithelial-mesenchymal transition have evoked novel therapeutic strategies aimed at halting the onset and progression of chronic renal fibrosis.