HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M700155-JLR200v1 49/1/66    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liang, C.-J. Articles by Ma, Y.-H. Search for Related Content PubMed PubMed Citation Articles by Liang, C.-J. Articles by Ma, Y.-H. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 49, 66-73, January 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

20-HETE inhibits the proliferation of vascular smooth muscle cells via transforming growth factor-β

Chan-Jung Liang^*, Harlan E. Ives, Chuen-Mao Yang^* and Yunn-Hwa Ma^1,*

^* Department of Physiology and Pharmacology, Center for Healthy Aging Research, Chang Gung University, Kuei-Shan, Tao-Yuan, Taiwan ROC
Department of Medicine, Division of Nephrology, University of California, San Francisco, CA

Published, JLR Papers in Press, October 4, 2007.

¹ To whom correspondence should be addressed. e-mail: yhma{at}mail.cgu.edu.tw

20-Hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P450 arachidonic acid metabolite, has been shown to modulate the growth of vascular smooth muscle cells (VSMCs). We asked whether 20-HETE modulates the proliferation of R22D cells, a clonal VSMC from neonatal rats, by releasing transforming growth factor-β (TGF-β). Incubation of R22D cells with 20-HETE for 24 h attenuated [³H]thymidine incorporation in a concentration-dependent manner without causing the release of lactate dehydrogenase. 20-HETE also inhibited platelet-derived growth factor (PDGF)-induced [³H]thymidine incorporation in R22D cells and human VSMCs. At 5 µM, 20-HETE reduced [³H]thymidine incorporation by 34 ± 6%; anti-TGF-β neutralizing antibody, but not nonspecific IgG, completely reversed the attenuated [³H]thymidine incorporation induced by 20-HETE. In addition, 20-HETE attenuated fetal bovine serum- and PDGF-induced expression of cyclin D1, a downstream effector of TGF-β₁, which was reversed by anti-TGF-β antibody. Further studies demonstrated that 20-HETE may increase TGF-β release to a level high enough to inhibit [³H]thymidine incorporation without altering the steady-state mRNA level of TGF-β. Nevertheless, pretreatment of indomethacin (a cyclooxygenase inhibitor) or paxilline (a potassium channel inhibitor) did not affect the inhibitory effect on DNA synthesis induced by 20-HETE. These results demonstrate for the first time a growth-inhibitory effect induced by 20-HETE, which may be mediated by TGF-β.

Supplementary key words 20-hydroxyeicosatetraenoic acid • cytochrome P450 • platelet-derived growth factor • DNA synthesis

Abbreviations: CDK, cyclin-dependent kinase; ECM, extracellular matrix; EPA, eicosapentaenoic acid; ERK 1/2, extracellular regulated protein kinase 1/2; FBS, fetal bovine serum; 20-HETE, 20-hydroxyeicosatetraenoic acid; LDH, lactate dehydrogenase; LTBP, latent TGF binding protein; MEK, MAPK/ERK kinase; MMP, matrix metalloprotease; PDGF, platelet-derived growth factor; TGF-β, transforming growth factor-β; VSMC, vascular smooth muscle cell

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. L. Karcher, D. O. Bayles, J. P. Bannantine, D. C. Beitz, and J. R. Stabel Osteopontin: A Novel Cytokine Involved in the Regulation of Mycobacterium avium subspecies paratuberculosis Infection in Periparturient Dairy Cattle J Dairy Sci, August 1, 2008; 91(8): 3079 - 3091. [Abstract] [Full Text] [PDF]

				F. Biasi, C. Mascia, and G. Poli The contribution of animal fat oxidation products to colon carcinogenesis, through modulation of TGF-{beta}1 signaling Carcinogenesis, May 1, 2008; 29(5): 890 - 894. [Abstract] [Full Text] [PDF]