The role of growth factors, cytokines, and vasoactive compounds in obstructive nephropathy.
Renal interstitial inflammation and fibrosis occurs after ureteral obstruction. Fibrosis most likely develops as a consequence of an imbalance between extracellular matrix synthesis and deposition and the degradation and removal of matrix. Angiotensin II is rapidly stimulated after the onset of ureteral obstruction. Angiotensin II in turn upregulates other factors (transforming growth factor beta, tumor necrosis factor-alpha, nuclear factor-kappaB, and several adhesion molecules and chemoattractants). Blockade of angiotensin II synthesis or inability of this peptide to bind to its receptor lessened the increased levels of mRNA for TGF-beta and collagen IV. Increased levels of angiotensin II have a major role in the development of tubulointerstitial fibrosis after ureteral obstruction.
Klahr
S
S
Department of Internal Medicine, Washington University School of Medicine, Saint Louis, MO, USA.
Morrissey
J J
JJ
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005355:Fibrosis; D006801:Humans; D007684:Kidney Tubules / Q000473:pathology*; D016328:NF-kappa B / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D011509:Proteoglycans / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014517:Ureteral Obstruction / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D014661:Vasoconstriction
C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D016328:NF-kappa B; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D009569:Nitric Oxide