title: Angiotensin II as a morphogenic cytokine stimulating renal fibrogenesis.
abstract: Inhibitors of the renin-angiotensin-aldosterone system attenuate glomerulosclerosis and interstitial fibrosis. Although the mechanisms underlying their antifibrotic effects are complex, angiotensin II (Ang II) emerges as a major profibrogenic cytokine. Ang II modulates renal cell growth, extracellular matrix synthesis, and degradation by multiple fibrotic pathways. One of the main targets of Ang II in renal fibrosis is TGFβ. Many, but not all, of the stimulatory effects of Ang II on fibrogenesis depend on the induction of TGFβ and its downstream mediators of matrix accumulation, inflammation, and apoptosis. However because of the difficulty in targeting TGFβ, connective tissue growth factor β (CTGF), a downstream mediator of TGFβ, has become a more promising antifibrotic target. Ang II can directly induce expression of renal CTGF and mediate epithelial-mesenchymal transition. Other profibrotic factors stimulated by Ang II include endothelin-1, plasminogen activator inhibitor-1, matrix metalloproteinase (MMP)-2, and a tissue inhibitor of metalloproteinase-2. Finally, connections among Ang II, hypoxia, and the induction of hypoxia-inducible factor-1α contribute to fibrogenesis. A better understanding of the multiple morphogenic effects of Ang II may be necessary to develop better strategies to halt the progression of renal disease.
authors: Department of Internal Medicine III, Friedrich Schiller University, Erlanger-Allee 101, D-07740 Jena, Germany.
authors: Christiane
authors: C
authors: Rüster
authors: Gunter
authors: G
authors: Wolf
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D055513:Connective Tissue Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D009400:Nephrosclerosis / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; C526317:CCN2 protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D055513:Connective Tissue Growth Factor