AJP - Renal Physiology, Vol 259, Issue 5 768-F777, Copyright © 1990 by American Physiological Society

ARTICLES

Angiotensin II induces cellular hypertrophy in cultured murine proximal tubular cells

G. Wolf and E. G. Neilson
Department of Medicine, University of Pennsylvania, Philadelphia 19104.

In the present study we demonstrate that a murine proximal tubular cell line (MCT cells), expressing angiotensin II (ANG II) receptors [dissociation constant (Kd) = 0.89 nM; receptor density (R0) = 46,900 receptors/cell] in culture, can be induced to hypertrophy after the daily addition of exogenous ANG II (10(-8) M). This hypertrophic response was characterized by an increase in total cellular protein content, by an enhancement of [3H]leucine incorporation into precipitable proteins, and by an augmentation in cell size by cytofluorography. This ANG II effect producing MCT cell enlargement was demonstrable in the absence of cellular proliferation. Proliferation of MCT cells, however, could be induced by epidermal growth factor (EGF) or platelet-derived growth factor (PDGF), and pretreatment of rested MCT cells with ANG II further enhanced EGF-induced cell division. ANG II-induced hypertrophy in MCT cells was factor specific, in that it could be blocked with saralasin, and not induced by angiotensin I (ANG I). This hypertrophic response was also independent of prostaglandin E2 synthesis but was transducible by pertussis toxin-sensitive G proteins and involved, to some extent, the activation of Na(+)-H+ exchange. ANG II, as well as EGF and/or PDGF, moreover, could induce the cellular oncogenes c-fos, c-myc, c-N-ras, but not c-cis, which suggests that early gene activation is probably not a specific prerequisite for hypertrophy. Our findings demonstrate that ANG II, in culture, can be a single-factor event capable of inducing hypertrophy in proximal tubular cells.

This article has been cited by other articles:

				D. Lasaitiene, Y. Chen, V. Mildaziene, Z. Nauciene, B. Sundelin, B. R. Johansson, M. Yano, and P. Friberg Tubular mitochondrial alterations in neonatal rats subjected to RAS inhibition Am J Physiol Renal Physiol, May 1, 2006; 290(5): F1260 - F1269. [Abstract] [Full Text] [PDF]

				D. Feliers, S. Duraisamy, J. L. Barnes, G. Ghosh-Choudhury, and B. S. Kasinath Translational regulation of vascular endothelial growth factor expression in renal epithelial cells by angiotensin II Am J Physiol Renal Physiol, March 1, 2005; 288(3): F521 - F529. [Abstract] [Full Text] [PDF]

				R. Gonzalez-Villalobos, R. B. Klassen, P. L. Allen, L. G. Navar, and T. G. Hammond Megalin binds and internalizes angiotensin II Am J Physiol Renal Physiol, February 1, 2005; 288(2): F420 - F427. [Abstract] [Full Text] [PDF]

				D. Lasaitiene, P. Friberg, B. Sundelin, and Y. Chen Neonatal RAS inhibition changes the phenotype of the developing thick ascending limb of Henle Am J Physiol Renal Physiol, June 1, 2004; 286(6): F1144 - F1153. [Abstract] [Full Text] [PDF]

				S.-L. Zhang, C. To, X. Chen, J. G. Filep, S.-S. Tang, J. R. Ingelfinger, and J. S. D. Chan Essential Role(s) of the Intrarenal Renin-Angiotensin System in Transforming Growth Factor-{beta}1 Gene Expression and Induction of Hypertrophy of Rat Kidney Proximal Tubular Cells in High Glucose J. Am. Soc. Nephrol., February 1, 2002; 13(2): 302 - 312. [Abstract] [Full Text] [PDF]

				A. C. Marsh, K. J. Gibson, J. Wu, P. C. Owens, J. A. Owens, and E. R. Lumbers Chronic effect of insulin-like growth factor I on renin synthesis, secretion, and renal function in fetal sheep Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2001; 281(1): R318 - R326. [Abstract] [Full Text] [PDF]

				D.-H. Kang, Y.-G. Kim, T. F. Andoh, K. L. Gordon, S.-I. Suga, M. Mazzali, J. A. Jefferson, J. Hughes, W. Bennett, G. F. Schreiner, et al. Post-cyclosporine-mediated hypertension and nephropathy: amelioration by vascular endothelial growth factor Am J Physiol Renal Physiol, April 1, 2001; 280(4): F727 - F736. [Abstract] [Full Text] [PDF]

				T. ECDER and R. W. SCHRIER Hypertension in Autosomal-Dominant Polycystic Kidney Disease: Early Occurrence and Unique Aspects J. Am. Soc. Nephrol., January 1, 2001; 12(1): 194 - 200. [Full Text]

				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]

				T. HANNKEN, R. SCHROEDER, G. ZAHNER, R. A. K. STAHL, and G. WOLF Reactive Oxygen Species Stimulate p44/42 Mitogen-Activated Protein Kinase and Induce p27Kip1: Role in Angiotensin II-Mediated Hypertrophy of Proximal Tubular Cells J. Am. Soc. Nephrol., August 1, 2000; 11(8): 1387 - 1397. [Abstract] [Full Text]

				S. J. Shankland and G. Wolf Cell cycle regulatory proteins in renal disease: role in hypertrophy, proliferation, and apoptosis Am J Physiol Renal Physiol, April 1, 2000; 278(4): F515 - F529. [Abstract] [Full Text] [PDF]

				D. C. Han, B. B. Hoffman, S. W. Hong, J. Guo, and F. N. Ziyadeh Therapy with antisense TGF-beta 1 oligodeoxynucleotides reduces kidney weight and matrix mRNAs in diabetic mice Am J Physiol Renal Physiol, April 1, 2000; 278(4): F628 - F634. [Abstract] [Full Text] [PDF]

				J. R. Ingelfinger, F. Jung, D. Diamant, L. Haveran, E. Lee, A. Brem, and S.-S. Tang Rat proximal tubule cell line transformed with origin-defective SV40 DNA: autocrine ANG II feedback Am J Physiol Renal Physiol, February 1, 1999; 276(2): F218 - F227. [Abstract] [Full Text] [PDF]

				T. Walther, D. Balschun, J.-P. Voigt, H. Fink, W. Zuschratter, C. Birchmeier, D. Ganten, and M. Bader Sustained Long Term Potentiation and Anxiety in Mice Lacking the Mas Protooncogene J. Biol. Chem., May 8, 1998; 273(19): 11867 - 11873. [Abstract] [Full Text] [PDF]

				M. I. Oliverio, K. Madsen, C. F. Best, M. Ito, N. Maeda, O. Smithies, and T. M. Coffman Renal growth and development in mice lacking AT1A receptors for angiotensin II Am J Physiol Renal Physiol, January 1, 1998; 274(1): F43 - F50. [Abstract] [Full Text] [PDF]

				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]

				Y. Ding, D. E. Stec, and C. D. Sigmund Genetic Evidence That Lethality in Angiotensinogen-deficient Mice Is Due to Loss of Systemic but Not Renal Angiotensinogen J. Biol. Chem., March 2, 2001; 276(10): 7431 - 7436. [Abstract] [Full Text] [PDF]