Angiotensin II and Renal Fibrosis

Abstract

Abstract-Angiotensin (Ang) II, the main peptide of the renin angiotensin system (RAS), is a renal growth factor, inducing hyperplasia/hypertrophy depending on the cell type. This vasoactive peptide activates mesangial and tubular cells and interstitial fibroblasts, increasing the expression and synthesis of extracellular matrix proteins. Some of these effects seem to be mediated by the release of other growth factors, such as TGF-␤. In experimental models of kidney damage, renal RAS activation, cell proliferation, and upregulation of growth factors and matrix production were described. In some of these models, blockade of Ang II actions by ACE inhibitors and angiotensin type 1 (AT 1 ) antagonists prevents proteinuria, gene expression upregulation, and fibrosis, as well as inflammatory cell infiltration. Interestingly, Ang II could also be involved in the fibrotic process because of its behavior as a proinflammatory cytokine, participating in various steps of the inflammatory response: Ang II (1) activates mononuclear cells and (2)

Effect of adrenotensin on cell proliferation is mediated by angiotensin II in cultured rat mesangial cells

“…The RAS plays an important role in the regulation of kidney functions and participates in the progression of renal damage through the modulation of cell growth, fibrosis and inflammation [11] . Ang II, a major effector molecule produced by the RAS, is critical for the development of renal fibrosis through the over-expression of growth factors, such as TGF-β1 and extracellular matrix (ECM) proteins [16] . Blockade of Ang II by angiotensin-converting enzyme (ACE) inhibitors or AT1 antagonists is one of the best options to treat renal diseases.…”

“…Ang II contributes to ECM accumulation [16] . TGF-β serves as a model profibrogenic cytokine [18] , and it is up-regulated in many fibrotic disorders that are associated with ECM accumulation, including human kidney diseases.…”

“…TGF-β serves as a model profibrogenic cytokine [18] , and it is up-regulated in many fibrotic disorders that are associated with ECM accumulation, including human kidney diseases. Ang II and TGF-β share some responses involved in matrix regulation [16] . Considerable experimental evidence has revealed that TGF-β is a mediator of Ang II actions.…”

Pathological Regression by Angiotensin II Type 1 Receptor Blockade in Patients with Mesangial Proliferative Glomerulonephritis

“…The diverse effects of angiotensin II on the kidney include 1) promotion of glomerular capillary hypertension due to efferent arteriole vasoconstriction (20,21), 2) stimulation of transforming growth factor-β (TGF-β) production by mesangial cells and tubular epithelial cells (22)(23)(24), 3) stimulation of matrix protein synthesis (23), 4) interstitial fibrosis (25,26), 5) mesangial cell growth (27,28), 6) changes of tubular epithelial cell phenotype and tubulointerstitial cell kinetics (29), 7) cytokine release from renal cells (30), and 8) activation of nuclear factor-κB (NF-κB) and increased monocyte chemoattractant protein-1 (MCP-1) gene expression on mesangial cells, leading to macrophage infiltration (10,31,32). These actions of angiotensin II are known to be the common pathway for several types of renal injury.…”

La fibrose tubulo-interstitielle rénale

“…Classiquement décrite comme un agent vasoactif, l'AngII est un peptide multifonctionnel qui exerce ses effets par la stimulation de deux récepteurs à sept domaines transmembranaires, les récepteurs AT 1 R et AT 2 R. Il est cependant couramment admis que l'AT 1 R relaie la plupart des effets classiques de l'AngII, et l'activation de l'AT 1 R par l'AngII est désormais considérée comme ayant un rôle-clé dans la progression de la FTI. En effet, l'AngII joue sur tous les tableaux de la fibrose (Figure 3) : elle participe directement à l'inflammation et au chimiotactisme en stimulant l'expression des molécules d'adhésion et la synthèse de chimiokines [23][24][25] ; elle exacerbe l'apparition des myofibroblastes en stimulant la TEM ainsi que la prolifération et la différenciation fibroblastiques [23][24][25][26] ; enfin, elle joue un rôle important dans l'accumulation de MEC en stimulant la synthèse de collagène I et de fibronectine par les myofibroblastes mais également en induisant l'expression de PAI-1 et de TIMP-1 [23,25].…”