The role of vasoactive compounds, growth factors and cytokines in the progression of renal disease.
A number of kidney diseases, and their progression to end-stage renal disease, are driven, in part, by the effects of angiotensin II. Increasing levels of angiotensin II may in turn up-regulate the expression of growth factors and cytokines, such as transforming growth factor-beta1 (TGF-beta1), tumor necrosis factor-alpha (TNF-alpha), osteopontin, vascular cell adhesion molecule-1 (VCAM-1), nuclear factor-kappaB (NF-kappaB), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and insulin-like growth factor. Most of these compounds promote cell growth and fibrosis. Angiotensin II also stimulates oxidative stress. This stress in turn may potentiate the vasoconstrictor effect of the peptide due, in part, to increased catabolism of nitric oxide (NO). Oxidative stress, fueled in part by angiotensin II, up-regulates the expression of adhesion molecules, chemoattractant compounds and cytokines. The angiotensinogen gene, which provides the precursor for angiotensin production, is stimulated by NF-kappaB activation. NF-kappaB is activated by angiotensin in the liver and in the kidney. This provides an autocrine reinforcing loop that up-regulates angiotensin production. Angiotensin II activates NF-kappaB through both AT1 and AT2 receptors. In addition, angiotensin-converting enzyme (ACE) inhibition markedly decreases NF-kappaB activation in the setting of renal disease.
Klahr
S
S
Department of Medicine, Washington University School of Medicine, Barnes-Jewish Hospital, St. Louis, Missouri 63110-1092, USA. sklahr@imgate.wustl.edu
Morrissey
J J
JJ
D000809:Angiotensins / Q000502:physiology*; D018450:Disease Progression; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D007674:Kidney Diseases / Q000150:complications*; D016328:NF-kappa B / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000809:Angiotensins; D006133:Growth Substances; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha