AJP - Heart Calcium Transients and Cell-Sarcomere
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 279: H2829-H2837, 2000;
0363-6135/00 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (29)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Douillet, C. D.
Right arrow Articles by Jaffa, A. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Douillet, C. D.
Right arrow Articles by Jaffa, A. A.
Vol. 279, Issue 6, H2829-H2837, December 2000

Mechanisms by which bradykinin promotes fibrosis in vascular smooth muscle cells: role of TGF-beta and MAPK

Christelle D. Douillet1, Victoria Velarde1, Julie T. Christopher1, Ronald K. Mayfield1,3, Maria E. Trojanowska1, and Ayad A. Jaffa1,2

Departments of 1 Medicine and 2 Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, and 3 Ralph H. Johnson Veteran Affairs Medical Center, Charleston, South Carolina 29425

Accumulation of extracellular matrix (ECM) is a hallmark feature of vascular disease. We have previously shown that hyperglycemia induces the expression of B2-kinin receptors in vascular smooth muscle cells (VSMC) and that bradykinin (BK) and hyperglycemia synergize to stimulate ECM production. The present study examined the cellular mechanisms through which BK contributes to VSMC fibrosis. VSMC treated with BK (10-8 M) for 24 h significantly increased alpha 2(I) collagen mRNA levels. In addition, BK produced a two- to threefold increase in alpha 2(I) collagen promoter activity in VSMC transfected with a plasmid containing the alpha 2(I) collagen promoter. Furthermore, treatment of VSMC with BK for 24 h produced a two- to threefold increase in the secretion rate of tissue inhibitor of metalloproteinase 1 (TIMP-1). The increase in alpha 2(I) collagen mRNA levels and alpha 2(I) collagen promoter activity, as well as TIMP-1 secretion, in response to BK were blocked by anti-transforming growth factor-beta (anti-TGF-beta ) neutralizing antibodies. BK (10-8 M) increased the endogenous production of TGF-beta 1 mRNA and protein levels. Inhibition of the mitogen-activated protein kinase (MAPK) pathway by PD-98059 inhibited the increase of alpha 2(I) collagen promoter activity, TIMP-1 production, and TGF-beta 1 protein levels observed in response to BK. These findings provide the first evidence that BK induces collagen type I and TIMP-1 production via autocrine activation of TGF-beta 1 and implicate MAPK pathway as a key player in VSMC fibrosis in response of BK.

collagen; tissue inhibitor of metalloproteinase 1; transforming growth factor-beta ; mitogen-activated protein kinase


This article has been cited by other articles:


Home page
 HypertensionHome page
J. Chao, H.-J. Li, Y.-Y. Yao, B. Shen, L. Gao, G. Bledsoe, and L. Chao
Kinin Infusion Prevents Renal Inflammation, Apoptosis, and Fibrosis via Inhibition of Oxidative Stress and Mitogen-Activated Protein Kinase Activity
Hypertension, March 1, 2007; 49(3): 490 - 497.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
N. S Hopkinson, K. I Eleftheriou, J. Payne, A. H Nickol, E. Hawe, J. Moxham, H. Montgomery, and M. I Polkey
+9/+9 Homozygosity of the bradykinin receptor gene polymorphism is associated with reduced fat-free mass in chronic obstructive pulmonary disease.
Am. J. Clinical Nutrition, April 1, 2006; 83(4): 912 - 917.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
M. Sohn, Y. Tan, B. Wang, R. L. Klein, M. Trojanowska, and A. A. Jaffa
Mechanisms of low-density lipoprotein-induced expression of connective tissue growth factor in human aortic endothelial cells
Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1624 - H1634.
[Abstract] [Full Text] [PDF]

Home page
 Ann Rheum DisHome page
A Del Rosso, O Distler, A F Milia, C Emanueli, L Ibba-Manneschi, S Guiducci, M L Conforti, S Generini, A Pignone, S Gay, et al.
Increased circulating levels of tissue kallikrein in systemic sclerosis correlate with microvascular involvement
Ann Rheum Dis, March 1, 2005; 64(3): 382 - 387.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
C. TSCHOPE, T. WALTHER, J. KONIGER, F. SPILLMANN, D. WESTERMANN, F. ESCHER, M. PAUSCHINGER, J. B. PESQUERO, M. BADER, H.-P. SCHULTHEISS, et al.
Prevention of cardiac fibrosis and left ventricular dysfunction in diabetic cardiomyopathy in rats by transgenic expression of the human tissue kallikrein gene
FASEB J, May 1, 2004; 18(7): 828 - 835.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
Y. Tan, F. N. Hutchison, and A. A. Jaffa
Mechanisms of angiotensin II-induced expression of B2 kinin receptors
Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H926 - H932.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
E. Cellier, M. Mage, J. Duchene, C. Pecher, R. Couture, J.-L. Bascands, and J.-P. Girolami
Bradykinin reduces growth factor-induced glomerular ERK1/2 phosphorylation
Am J Physiol Renal Physiol, February 1, 2003; 284(2): F282 - F292.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
H. A. Baptista, M. C. W. Avellar, R. C. Araujo, J. L. Pesquero, J. P. Schanstra, J. L. Bascands, J. P. Esteve, A. C. M. Paiva, M. Bader, and J. B. Pesquero
Transcriptional Regulation of the Rat Bradykinin B2 Receptor Gene: Identification of a Silencer Element
Mol. Pharmacol., December 1, 2002; 62(6): 1344 - 1355.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. Christopher, V. Velarde, D. Zhang, D. Mayfield, R. K. Mayfield, and A. A. Jaffa
Regulation of B2-kinin receptors by glucose in vascular smooth muscle cells
Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1537 - H1546.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online