AJP - Renal Physiology, Vol 261, Issue 1 117-F125, Copyright © 1991 by American Physiological Society

ARTICLES

Regulated expression of endothelin 1 in glomerular capillary endothelial cells

P. A. Marsden, D. M. Dorfman, T. Collins, B. M. Brenner, S. H. Orkin and B. J. Ballermann
Harvard Center for the Study of Kidney Diseases, Brigham and Women's Hospital, Boston, Massachusetts.

Endothelin (ET)-1 is a powerful vasoconstrictor known to be produced and secreted by endothelial cells lining large vessels. Because ET-1 stimulates glomerular mesangial cell contraction, glomerular capillary endothelial cells (GEN), normally situated in close apposition to mesangial cells, were examined for potential ET expression and secretion. Cultured bovine GEN released ET in a time-dependent fashion. ET secretion was significantly stimulated by bradykinin, an agonist known to activate phospholipase C in these cells. Preproendothelin 1 (preproET-1) mRNA levels in GEN rose in a biphasic manner on stimulation with bradykinin. The early increments (at 30 min) were not dependent on new protein synthesis, whereas the late rise (6 h after addition of bradykinin) appeared to be protein synthesis dependent. Neither early or late bradykinin-stimulated preproET-1 mRNA expression in glomerular endothelial cells was due to inhibition of mRNA breakdown. Both phases of preproET-1 mRNA expression were observed with other glomerular endothelial cell calcium-mobilizing agonists, namely thrombin, and were mimicked by the calcium ionophore ionomycin. By contrast, the protein kinase C activator phorbol myristate acetate only enhanced preproET-1 mRNA expression at 30 min and suppressed expression thereafter. It is concluded that GEN have the potential to express and secrete ET-1 in a phospholipase C-regulated fashion. Furthermore, because glomerular mesangial cells respond to this peptide, the findings raise the possibility of paracrine regulation of mesangial cell tone by glomerular endothelial cell-derived ET-1.

This article has been cited by other articles:

				J. M. Williams, X. Zhao, M. H. Wang, J. D. Imig, and D. M. Pollock Peroxisome Proliferator-Activated Receptor-{alpha} Activation Reduces Salt-Dependent Hypertension During Chronic Endothelin B Receptor Blockade Hypertension, August 1, 2005; 46(2): 366 - 371. [Abstract] [Full Text] [PDF]

				S.-D. Lee, D.-S. Lee, Y.-G. Chun, T.-S. Shim, C.-M. Lim, Y. Koh, W.-S. Kim, D.-S. Kim, and W.-D. Kim Cigarette smoke extract induces endothelin-1 via protein kinase C in pulmonary artery endothelial cells Am J Physiol Lung Cell Mol Physiol, August 1, 2001; 281(2): L403 - L411. [Abstract] [Full Text] [PDF]

				M. FOSCHI, A. SOROKIN, P. PRATT, A. MCGINTY, G. L. VILLA, F. FRANCHI, and M. J. DUNN PreproEndothelin-1 Expression in Human Mesangial Cells: Evidence for a p38 Mitogen-Activated Protein Kinase/Protein Kinases-C--Dependent Mechanism J. Am. Soc. Nephrol., June 1, 2001; 12(6): 1137 - 1150. [Abstract] [Full Text]

				J. Navarro-Antolin, J. Rey-Campos, and S. Lamas Transcriptional Induction of Endothelial Nitric Oxide Gene by Cyclosporine A. A ROLE FOR ACTIVATOR PROTEIN-1 J. Biol. Chem., February 4, 2000; 275(5): 3075 - 3080. [Abstract] [Full Text] [PDF]

				H. Berthold, K. Munter, A. Just, H. R. Kirchheim, and H. Ehmke Contribution of endothelin to renal vascular tone and autoregulation in the conscious dog Am J Physiol Renal Physiol, March 1, 1999; 276(3): F417 - F424. [Abstract] [Full Text] [PDF]

				J. A. Dlugosz, S. Munk, X. Zhou, and C. I. Whiteside Endothelin-1-induced mesangial cell contraction involves activation of protein kinase C-alpha , -delta , and -epsilon Am J Physiol Renal Physiol, September 1, 1998; 275(3): F423 - F432. [Abstract] [Full Text] [PDF]

				J. D. STOCKAND and S. C. SANSOM Glomerular Mesangial Cells: Electrophysiology and Regulation of Contraction Physiol Rev, July 1, 1998; 78(3): 723 - 744. [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]

				J. A. Dlugosz, S. Munk, E. Ispanovic, H. J. Goldberg, and C. I. Whiteside Mesangial cell filamentous actin disassembly and hypocontractility in high glucose are mediated by PKC-zeta Am J Physiol Renal Physiol, January 1, 2002; 282(1): F151 - F163. [Abstract] [Full Text] [PDF]