Journal of the American Society of Nephrology, Vol 3, 1531-1540, Copyright © 1993 by American Society of Nephrology

REVIEWS

Angiotensin II as a renal growth factor

G Wolf and EG Neilson

Angiotensin II (ANG II) can have multiple effects on the kidney, including influences on the regulation of glomerular hemodynamics and tubular transport as well as consequences for the glomerular processing of macromolecules. The recognized suppressive effects of angiotensin- converting enzyme inhibitors on compensatory renal growth, even in the absence of hemodynamic effects, and the well-documented proliferative effect of ANG II on vascular smooth muscle cells have provided the background for the recent intensive interest in this peptide as a renal cytokine. Diverse cell types along the nephron express a variety of ANG II receptors. These receptors and their putative signal transduction pathways have been best characterized in mesangial and proximal tubular cells. Culture experiments provide convincing evidence that ANG II can be a phenotypic influence on these cell types. The growth responses and the associated signal transduction pathways, however, are different in mesangial and proximal tubular cells. These ANG II-mediated responses are also associated with an increase in the synthesis of distinct collagen subtypes, potentially linking the growth stimulatory effects of ANG II to the irreversible changes of glomerulosclerosis and tubulointerstitial fibrosis observed in chronic renal failure. Preventing the intrarenal actions of ANG II with angiotensin-converting enzyme inhibitors or with the new, orally active, selective ANG II receptor antagonists may provide a rational therapeutic approach to attenuate the progression of a variety of kidney diseases.

This article has been cited by other articles:

				S. R. Holdsworth and S. A. Summers Role of Mast Cells in Progressive Renal Diseases J. Am. Soc. Nephrol., December 1, 2008; 19(12): 2254 - 2261. [Abstract] [Full Text] [PDF]

				I. Kolesnyk, M. Noordzij, F. W. Dekker, E. W. Boeschoten, and R. T. Krediet A positive effect of AII inhibitors on peritoneal membrane function in long-term PD patients Nephrol. Dial. Transplant., July 30, 2008; (2008) gfn421v1. [Abstract] [Full Text] [PDF]

				P. Vieitez, O. Gomez, E. R Uceda, M. E. Vera, and E. Molina-Holgado Systemic and local effects of angiotensin II blockade in experimental diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System, June 1, 2008; 9(2): 96 - 102. [Abstract] [PDF]

				A. Sachse and G. Wolf Angiotensin II Induced Reactive Oxygen Species and the Kidney J. Am. Soc. Nephrol., September 1, 2007; 18(9): 2439 - 2446. [Abstract] [Full Text] [PDF]

				R. R. Singh, K. M. Moritz, J. F. Bertram, and L. A. Cullen-McEwen Effects of dexamethasone exposure on rat metanephric development: in vitro and in vivo studies Am J Physiol Renal Physiol, August 1, 2007; 293(2): F548 - F554. [Abstract] [Full Text] [PDF]

				Y. Takeuchi, K. Yamauchi, J. Nakamura, S. Shigematsu, and K. Hashizume Angiotensin II regulates migration in mouse cultured mesangial cells: evidence for the presence of receptor subtype-specific regulation. J. Endocrinol., November 1, 2006; 191(2): 361 - 367. [Abstract] [Full Text] [PDF]

				K. A. Griffin and A. K. Bidani Progression of Renal Disease: Renoprotective Specificity of Renin-Angiotensin System Blockade Clin. J. Am. Soc. Nephrol., September 1, 2006; 1(5): 1054 - 1065. [Abstract] [Full Text] [PDF]

				M. B. Marrero, A. K. Banes-Berceli, D. M. Stern, and D. C. Eaton Role of the JAK/STAT signaling pathway in diabetic nephropathy Am J Physiol Renal Physiol, April 1, 2006; 290(4): F762 - F768. [Abstract] [Full Text] [PDF]

				J. L. Faulkner, L. M. Szcykalski, F. Springer, and J. L. Barnes Origin of Interstitial Fibroblasts in an Accelerated Model of Angiotensin II-Induced Renal Fibrosis Am. J. Pathol., November 1, 2005; 167(5): 1193 - 1205. [Abstract] [Full Text] [PDF]

				J. M. Forbes, S. R. Thorpe, V. Thallas-Bonke, J. Pete, M. C. Thomas, E. R. Deemer, S. Bassal, A. El-Osta, D. M. Long, S. Panagiotopoulos, et al. Modulation of Soluble Receptor for Advanced Glycation End Products by Angiotensin-Converting Enzyme-1 Inhibition in Diabetic Nephropathy J. Am. Soc. Nephrol., August 1, 2005; 16(8): 2363 - 2372. [Abstract] [Full Text] [PDF]

				L. Y.Y. Chan, J. C.K. Leung, S. C.W. Tang, C. B.Y. Choy, and K. N. Lai Tubular Expression of Angiotensin II Receptors and Their Regulation in IgA Nephropathy J. Am. Soc. Nephrol., August 1, 2005; 16(8): 2306 - 2317. [Abstract] [Full Text] [PDF]

				A. A. Banday, A. H. Siddiqui, M. M. Menezes, and T. Hussain Insulin treatment enhances AT1 receptor function in OK cells Am J Physiol Renal Physiol, June 1, 2005; 288(6): F1213 - F1219. [Abstract] [Full Text] [PDF]

				K. Chen, L. C. Carey, J. Liu, N. K. Valego, S. B. Tatter, and J. C. Rose The effect of hypothalamo-pituitary disconnection on the renin-angiotensin system in the late-gestation fetal sheep Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2005; 288(5): R1279 - R1287. [Abstract] [Full Text] [PDF]

				B. E. Thomas and T. J. Thekkumkara Glucose Mediates Transcriptional Repression of the Human Angiotensin Type-1 Receptor Gene: Role for a Novel Cis-acting Element Mol. Biol. Cell, October 1, 2004; 15(10): 4347 - 4355. [Abstract] [Full Text] [PDF]

				J. Ma, T. Matsusaka, H. Yang, H. Kawachi, F. Shimizu, Y. Isaka, E. Imai, V. Kon, and I. Ichikawa Local Actions of Endogenous Angiotensin II in Injured Glomeruli J. Am. Soc. Nephrol., May 1, 2004; 15(5): 1268 - 1276. [Abstract] [Full Text] [PDF]

				T. Naito, T. Masaki, D. J. Nikolic-Paterson, C. Tanji, N. Yorioka, and N. Kohno Angiotensin II induces thrombospondin-1 production in human mesangial cells via p38 MAPK and JNK: a mechanism for activation of latent TGF-{beta}1 Am J Physiol Renal Physiol, February 1, 2004; 286(2): F278 - F287. [Abstract] [Full Text] [PDF]

				S. I. McFarlane, N. Winer, and J. R. Sowers Role of the Natriuretic Peptide System in Cardiorenal Protection Arch Intern Med, December 8, 2003; 163(22): 2696 - 2704. [Abstract] [Full Text] [PDF]

				K.-Y. K. Mok, K. Sandberg, J. M. Sweeny, W. Zheng, S. Lee, and S. E. Mulroney Growth hormone regulation of glomerular AT1 angiotensin receptors in adult uninephrectomized male rats Am J Physiol Renal Physiol, December 1, 2003; 285(6): F1085 - F1091. [Abstract] [Full Text]

				M. Ruperez, M. Ruiz-Ortega, V. Esteban, O. Lorenzo, S. Mezzano, J. J. Plaza, and J. Egido Angiotensin II Increases Connective Tissue Growth Factor in the Kidney Am. J. Pathol., November 1, 2003; 163(5): 1937 - 1947. [Abstract] [Full Text] [PDF]

				B. Yuan, M. Liang, Z. Yang, E. Rute, N. Taylor, M. Olivier, and A. W. Cowley Jr. Gene expression reveals vulnerability to oxidative stress and interstitial fibrosis of renal outer medulla to nonhypertensive elevations of ANG II Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2003; 284(5): R1219 - R1230. [Abstract] [Full Text] [PDF]

				K. M. Moritz, K. Johnson, R. Douglas-Denton, E. M. Wintour, and M. Dodic Maternal Glucocorticoid Treatment Programs Alterations in the Renin-Angiotensin System of the Ovine Fetal Kidney Endocrinology, November 1, 2002; 143(11): 4455 - 4463. [Abstract] [Full Text] [PDF]

				J. M. Forbes, M. E. Cooper, V. Thallas, W. C. Burns, M. C. Thomas, G. C. Brammar, F. Lee, S. L. Grant, L. A. Burrell, G. Jerums, et al. Reduction of the Accumulation of Advanced Glycation End Products by ACE Inhibition in Experimental Diabetic Nephropathy Diabetes, November 1, 2002; 51(11): 3274 - 3282. [Abstract] [Full Text] [PDF]

				G. Ding, K. Reddy, A. A. Kapasi, N. Franki, N. Gibbons, B. S. Kasinath, and P. C. Singhal Angiotensin II induces apoptosis in rat glomerular epithelial cells Am J Physiol Renal Physiol, July 1, 2002; 283(1): F173 - F180. [Abstract] [Full Text] [PDF]

				O. Lorenzo, M. Ruiz-Ortega, P. Esbrit, M. Ruperez, A. Ortega, S. Santos, J. Blanco, L. Ortega, and J. Egido Angiotensin II Increases Parathyroid Hormone-Related Protein (PTHrP) and the Type 1 PTH/PTHrP Receptor in the Kidney J. Am. Soc. Nephrol., June 1, 2002; 13(6): 1595 - 1607. [Abstract] [Full Text] [PDF]

				A. J. Edgley, N. R. Nichols, and W. P. Anderson Acute intrarenal infusion of ANG II does not stimulate immediate early gene expression in the kidney Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2002; 282(4): R1133 - R1139. [Abstract] [Full Text] [PDF]

				I. L. Noronha, C. K. Fujihara, and R. Zatz The inflammatory component in progressive renal disease--are interventions possible? Nephrol. Dial. Transplant., March 1, 2002; 17(3): 363 - 368. [Full Text] [PDF]

				M. NORIS, N. AZZOLLINI, A. PEZZOTTA, M. MISTER, A. BENIGNI, G. MARCHETTI, E. GAGLIARDINI, N. PERICO, and G. REMUZZI Combined Treatment with Mycophenolate Mofetil and an Angiotensin II Receptor Antagonist Fully Protects from Chronic Rejection in a Rat Model of Renal Allograft J. Am. Soc. Nephrol., September 1, 2001; 12(9): 1937 - 1946. [Abstract] [Full Text] [PDF]

				S. A. Mezzano, M. Ruiz-Ortega, and J. Egido Angiotensin II and Renal Fibrosis Hypertension, September 1, 2001; 38(3): 635 - 638. [Abstract] [Full Text] [PDF]

				G. A. Cinotti and P. C. Zucchelli Effect of Lisinopril on the progression of renal insufficiency in mild proteinuric non-diabetic nephropathies Nephrol. Dial. Transplant., May 1, 2001; 16(5): 961 - 966. [Abstract] [Full Text] [PDF]

				M. Ruiz-Ortega, O. Lorenzo, M. Ruperez, J. Blanco, and J. Egido Systemic Infusion of Angiotensin II into Normal Rats Activates Nuclear Factor-{{kappa}}B and AP-1 in the Kidney : Role of AT1 and AT2 Receptors Am. J. Pathol., May 1, 2001; 158(5): 1743 - 1756. [Abstract] [Full Text] [PDF]

				A. B. M. Nilsson, N. Nitescu, Y. Chen, G. S. Guron, N. Marcussen, G. L. Matejka, and P. Friberg IGF-I treatment attenuates renal abnormalities induced by neonatal ACE inhibition Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2000; 279(3): R1050 - R1060. [Abstract] [Full Text] [PDF]

				P. Esbrit and J. Egido The emerging role of parathyroid hormone-related protein as a renal regulating factor Nephrol. Dial. Transplant., August 1, 2000; 15(8): 1109 - 1111. [Full Text] [PDF]

				M. Ruiz-Ortega, O. Lorenzo, M. Ruperez, and J. Egido ACE inhibitors and AT1 receptor antagonists--beyond the haemodynamic effect Nephrol. Dial. Transplant., May 1, 2000; 15(5): 561 - 565. [Full Text] [PDF]

				G. GURON, N. MARCUSSEN, A. NILSSON, B. SUNDELIN, and P. FRIBERG Postnatal Time Frame for Renal Vulnerability to Enalapril in Rats J. Am. Soc. Nephrol., July 1, 1999; 10(7): 1550 - 1560. [Abstract] [Full Text]

				S. Mentzel, H.B.P.M. Dijkman, J.P.H.F. van Son, J.F.M. Wetzels, and K.J.M. Assmann In Vivo Antibody-mediated Modulation of Aminopeptidase A in Mouse Proximal Tubular Epithelial Cells J. Histochem. Cytochem., January 1, 1999; 47(7): 871 - 880. [Abstract] [Full Text]

				T. Yoshioka, Y.-x. Xu, H. Yoshida, H. Shiraga, T. Muraki, and K. Ito Deletion polymorphism of the angiotensin converting enzyme gene predicts persistent proteinuria in Henoch-Schonlein purpura nephritis Arch. Dis. Child., November 1, 1998; 79(5): 394 - 399. [Abstract] [Full Text]

				G. Guron, N. Marcussen, and P. Friberg Urinary acidification and net acid excretion in adult rats treated neonatally with enalapril Am J Physiol Regulatory Integrative Comp Physiol, June 1, 1998; 274(6): R1718 - R1724. [Abstract] [Full Text] [PDF]

				F. Otsuka, T. Yamauchi, H. Kataoka, Y. Mimura, T. Ogura, and H. Makino Effects of chronic inhibition of ACE and AT1 receptors on glomerular injury in Dahl salt-sensitive rats Am J Physiol Regulatory Integrative Comp Physiol, June 1, 1998; 274(6): R1797 - R1806. [Abstract] [Full Text] [PDF]

				M. S. Ali, B. Schieffer, P. Delafontaine, K. E. Bernstein, B. N. Ling, and M. B. Marrero Angiotensin II Stimulates Tyrosine Phosphorylation and Activation of Insulin Receptor Substrate 1 and Protein-tyrosine Phosphatase 1D in Vascular Smooth Muscle Cells J. Biol. Chem., May 9, 1997; 272(19): 12373 - 12379. [Abstract] [Full Text] [PDF]

				K. J. McLaughlin, P. N. Harden, S. Ueda, J. M. Boulton-Jones, J. M.C. Connell, and A. G. Jardine The Role of Genetic Polymorphisms of Angiotensin-Converting Enzyme in the Progression of Renal Diseases Hypertension, November 1, 1996; 28(5): 912 - 915. [Abstract] [Full Text]

				G. Wolf, F. N. Ziyadeh, G. Zahner, and R. A.K. Stahl Angiotensin II Is Mitogenic for Cultured Rat Glomerular Endothelial Cells Hypertension, April 1, 1996; 27(4): 897 - 905. [Abstract] [Full Text]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673