Mechanisms of Interstitial Fibrosis in Obstructive Nephropathy

Numerous pathological processes are involved in the renal tubulointerstitial fibrogenic reaction that occurs after ureteral ligation. Central to these maladaptive events is a florid interstitial monocytic infiltration of the tubulointerstitium, which is preceded by a proximal tubular up-regulation of macrophage chemoattractants. Once within the peritubular and periglomerular space, these macrophages are capable of releasing a potent armamentarium of peptide growth factors. TGF-beta has been singled out as a pivotal growth factor mediating fibrogenesis owing to its multifaceted effects on fibroblasts, tubular cells, matrix metalloproteinases, and TIMPs. A growing body of experimental studies using the rat hydronephrosis model is now demonstrating that angiotensin II may, in addition to its well-known hemodynamic effect, also be pro-inflammatory and pro-fibrogenic.