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.
Diamond
J R
JR
Division of Nephrology, Pennsylvania State University, College of Medicine, Hershey 17033, USA.
Ricardo
S D
SD
Klahr
S
S
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D007684:Kidney Tubules / Q000473:pathology*; D053495:Osteopontin; D051381:Rats; D012084:Renin-Angiotensin System / Q000502:physiology; D012795:Sialoglycoproteins / Q000502:physiology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D014517:Ureteral Obstruction / Q000473:pathology*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D053495:Osteopontin