Role of tubul epithelial cells in the pathogenesis of tubulointerstitial fibrosis induced by glomerular

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Abstract
Tubulointerstitial fibrosis is a final common pathway for progressive renal injury in most 'inflammatory' and 'non-inflammatory' glomerulopathies. Indeed, the level of tubulointerstitial fibrosis correlates closely with the degree of chronic renal dysfunction in these settings. An emerging body of evidence suggests that tubule epithelial cells are dynamic players in the pathogenesis of tubulointerstitial fibrosis. Here we briefly review the potential mechanisms of tubule cell activation in patients with glomerular disease. These mechanisms include: (a) direct involvement of glomerular and tubulointerstitial compartments by the primary disease; (b) secondary activation of tubule epithelial cells by glomerulus-derived cytokines; (c) perturbation of tubule epithelial cell function by plasma proteins and associated moieties filtered in excess through injured glomeruli; (d) tubulointerstitial ischaemia downstream to glomerular injury; and (e) hyperfunction of remnant tubules. Activated tubule epithelial cells are, in turn, a rich source of cytokines, chemokines and other mediators that promote leukocyte recruitment, cytotoxicity and fibrogenesis, thereby establishing a 'vicious cycle' of tubulointerstitial injury. The further delineation of the role played by the tubule epithelial cell in the pathogenesis of tubulointerstitial fibrosis may suggest novel approaches for the treatment of progressive renal diseases.