Role of angiotensin II in tubulointerstitial injury.
The renin angiotensin system (RAS) has been implicated in tubulointerstitial injury in a range of clinical and experimental settings. Angiotensin II, the major effector molecule of the RAS, in addition to its effects on systemic blood pressure and intrarenal hemodynamics, also acts as a local hormone and growth factor to modulate renal function and pathology. There is increasing evidence for a pivotal role of this hormone in influencing renal tubular and interstitial function and structure including regulation of multiple cytokines and chemokines, promoting infiltration of monocytes/macrophages, promoting cellular proliferation, and inducing apoptosis. Pathologic actions of angiotensin II lead to tubulointerstitial fibrosis and inflammation via a range of cytokines and chemokines including transforming growth factor (TNF)-beta1, osteopontin, tumor necrosis factor (TNF)-alpha, secreted protein acidic and rich in cysteine (SPARC), and RANTES (regulated on activation normal T-cell expression and secreted). Blockade of production of angiotensin II by an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor antagonism with an angiotensin type 1 receptor antagonist has been shown to attenuate tubulointerstitial injury and reduce expression of cytokines and matrix proteins. The role of angiotensin II in tubulointerstitial fibrosis and inflammation is addressed in this article.
Cao
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Department of Medicine, University of Melbourne, Austin, Australia.
Cooper
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D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D018946:Chemokine CCL5 / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D006801:Humans; D007684:Kidney Tubules / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology; D009395:Nephritis, Interstitial / Q000378:metabolism / Q000473:pathology*; D015676:Osteonectin / Q000502:physiology; D053495:Osteopontin; D012084:Renin-Angiotensin System / Q000502:physiology*; D012795:Sialoglycoproteins / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D018946:Chemokine CCL5; D016207:Cytokines; D016328:NF-kappa B; D015676:Osteonectin; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D053495:Osteopontin; D000804:Angiotensin II