This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Horio, T. Articles by Kangawa, K. Search for Related Content PubMed PubMed Citation Articles by Horio, T. Articles by Kangawa, K.

Gene Expression, Secretion, and Autocrine Action of C-Type Natriuretic Peptide in Cultured Adult Rat Cardiac Fibroblasts

Department of Medicine (T.H., F.Y., Y.K.) and Research Institute (T.T., T.M., S.S., K.K.), National Cardiovascular Center, Suita, Osaka 565-8565, Japan; Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine (T.N.), Tochigi 321-0293, Japan; and Institute of Life Sciences, Kurume University (M.K.), Kurume, Fukuoka 839-0861, Japan

Address all correspondence and requests for reprints to: Takeshi Horio, M.D., Division of Hypertension and Nephrology, Department of Medicine, National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan. E-mail: thorio{at}ri.ncvc.go.jp.

C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is known to be synthesized in the central nervous system and vascular endothelial cells, in contrast to atrial natriuretic peptide and brain natriuretic peptide. However, there have been no studies concerning CNP production in cultured cardiac cells. Here, we examined the production and the local effect of CNP in cultured ventricular cells. Under serum-free conditions, adult rat cardiac fibroblasts secreted immunoreactive CNP time dependently. TGF-ß1, basic fibroblast growth factor, and endothelin-1 significantly stimulated CNP secretion. Northern blot analysis detected significant expressions of CNP and its specific receptor (guanylyl cyclase-B) mRNA in cardiac fibroblasts. CNP stimulated intracellular cGMP production in fibroblasts more intensely than atrial and brain natriuretic peptides. CNP inhibited both DNA and collagen syntheses of cardiac fibroblasts, and these inhibitory effects by CNP were stronger than by atrial and brain natriuretic peptides. The inhibition by CNP of DNA and collagen syntheses was reproduced by a cGMP analog, 8-bromo cGMP. The present findings demonstrate that CNP is synthesized in and secreted from cardiac fibroblasts and suggest that CNP has a suppressive effect on fibroblast proliferation and extracellular matrix production, probably via the guanylyl cyclase-B-mediated cGMP-dependent process. CNP produced by cardiac fibroblasts may play a role as an autocrine regulator against excessive cardiac fibrosis.

This article has been cited by other articles:

				O. Lisy, B. K. Huntley, D. J. McCormick, P. A. Kurlansky, and J. C. Burnett Jr Design, Synthesis, and Actions of a Novel Chimeric Natriuretic Peptide: CD-NP. J. Am. Coll. Cardiol., July 1, 2008; 52(1): 60 - 68. [Abstract] [Full Text] [PDF]

				R. A. Rose and W. R. Giles Natriuretic peptide C receptor signalling in the heart and vasculature J. Physiol., January 15, 2008; 586(2): 353 - 366. [Abstract] [Full Text] [PDF]

				B. S. Hu, L. K. Landeen, N. Aroonsakool, and W. R. Giles An analysis of the effects of stretch on IGF-I secretion from rat ventricular fibroblasts Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H677 - H683. [Abstract] [Full Text] [PDF]

				R. A. Rose, N. Hatano, S. Ohya, Y. Imaizumi, and W. R. Giles C-type natriuretic peptide activates a non-selective cation current in acutely isolated rat cardiac fibroblasts via natriuretic peptide C receptor-mediated signalling J. Physiol., April 1, 2007; 580(1): 255 - 274. [Abstract] [Full Text] [PDF]

				M. Wakeno, T. Minamino, O. Seguchi, H. Okazaki, O. Tsukamoto, K.-i. Okada, A. Hirata, M. Fujita, H. Asanuma, J. Kim, et al. Long-Term Stimulation of Adenosine A2b Receptors Begun After Myocardial Infarction Prevents Cardiac Remodeling in Rats Circulation, October 31, 2006; 114(18): 1923 - 1932. [Abstract] [Full Text] [PDF]

				M. D. Jarvis, M. T. Rademaker, L. J. Ellmers, M. J. Currie, J. L. McKenzie, B. R. Palmer, C. M. Frampton, A. M. Richards, and V. A. Cameron Comparison of infarct-derived and control ovine cardiac myofibroblasts in culture: response to cytokines and natriuretic peptide receptor expression profiles. Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1952 - H1958. [Abstract] [Full Text] [PDF]

				T. E. H. Christoffersen, M. Aplin, C. C. Strom, S. P. Sheikh, O. Skott, P. K. Busk, S. Haunso, and L. B. Nielsen Increased natriuretic peptide receptor A and C gene expression in rats with pressure-overload cardiac hypertrophy Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1635 - H1641. [Abstract] [Full Text] [PDF]

				T. H. Langenickel, J. Buttgereit, I. Pagel-Langenickel, M. Lindner, J. Monti, K. Beuerlein, N. Al-Saadi, R. Plehm, E. Popova, J. Tank, et al. Cardiac hypertrophy in transgenic rats expressing a dominant-negative mutant of the natriuretic peptide receptor B PNAS, March 21, 2006; 103(12): 4735 - 4740. [Abstract] [Full Text] [PDF]

				T. Nishikimi, N. Maeda, and H. Matsuoka The role of natriuretic peptides in cardioprotection Cardiovasc Res, February 1, 2006; 69(2): 318 - 328. [Abstract] [Full Text] [PDF]

				D. Rahmutula and D. G. Gardner C-Type Natriuretic Peptide Down-Regulates Expression of Its Cognate Receptor in Rat Aortic Smooth Muscle Cells Endocrinology, November 1, 2005; 146(11): 4968 - 4974. [Abstract] [Full Text] [PDF]

				T. Tokudome, T. Horio, I. Kishimoto, T. Soeki, K. Mori, Y. Kawano, M. Kohno, D. L. Garbers, K. Nakao, and K. Kangawa Calcineurin-Nuclear Factor of Activated T Cells Pathway-Dependent Cardiac Remodeling in Mice Deficient in Guanylyl Cyclase A, a Receptor for Atrial and Brain Natriuretic Peptides Circulation, June 14, 2005; 111(23): 3095 - 3104. [Abstract] [Full Text] [PDF]

				T. Soeki, I. Kishimoto, H. Okumura, T. Tokudome, T. Horio, K. Mori, and K. Kangawa C-type natriuretic peptide, a novel antifibrotic and antihypertrophic agent, prevents cardiac remodeling after myocardial infarction J. Am. Coll. Cardiol., February 15, 2005; 45(4): 608 - 616. [Abstract] [Full Text] [PDF]

				S. Murakami, N. Nagaya, T. Itoh, T. Fujii, T. Iwase, K. Hamada, H. Kimura, and K. Kangawa C-type natriuretic peptide attenuates bleomycin-induced pulmonary fibrosis in mice Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1172 - L1177. [Abstract] [Full Text] [PDF]

				T. Tokudome, T. Horio, T. Soeki, K. Mori, I. Kishimoto, S.-i. Suga, F. Yoshihara, Y. Kawano, M. Kohno, and K. Kangawa Inhibitory Effect of C-Type Natriuretic Peptide (CNP) on Cultured Cardiac Myocyte Hypertrophy: Interference between CNP and Endothelin-1 Signaling Pathways Endocrinology, May 1, 2004; 145(5): 2131 - 2140. [Abstract] [Full Text] [PDF]