Sustained Contraction and Loss of No Production in Tgfbeta1-treated Endothelial Cells.
From: Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
British journal of pharmacology
- Publish Date: Oct 2006
- ISSN: 0007-1188
- Volume: 149
- Issue: 4
- Pages: 355-64
- Medium: Print
- Language: English
- Citation (JAMA): Watanabe M, Oike M, Ohta Y, et al. Sustained Contraction and Loss of No Production in Tgfbeta1-treated Endothelial Cells.. Br. J. Pharmacol. Oct 2006;149:355-64
Abstract
BACKGROUND AND PURPOSE: Transforming growth factor beta1 (TGFbeta1) is generated in atherosclerotic and injured vessel walls. We examined whether the endothelial-to-mesenchymal transdifferentiation induced by TGFbeta1 affects endothelial functions. EXPERIMENTAL APPROACH: Bovine aortic endothelial cells (BAECs) were treated with 3 ng ml(-1) TGFbeta1 for 7 days. Contraction of TGFbeta1-treated BAECs was assessed by collagen gel contraction assay. Protein expression and phosphorylation were assessed by Western blotting. Intracellular Ca2+ concentration and NO production were measured using fura2 and DAF-2, respectively. KEY RESULTS: TGFbeta1-treated BAECs showed dense actin fibers and expressed smooth muscle marker proteins; they also changed into smooth muscle-like, spindle-shaped cells in collagen gel cultures. ATP (10 microM) induced a gradual contraction of collagen gels containing TGFbeta1-treated BAECs but not of gels containing control BAECs. ATP-induced contraction of TGFbeta1-treated BAECs was not reversed by the removal of ATP but was partially suppressed by a high concentration of sodium nitroprusside (1 microM). TGFbeta1-treated BAECs showed sustained phosphorylation of myosin light chain in response to ATP and low levels of basal MYPT1 expression. ATP-induced Ca2+ transients as well as eNOS protein expression were not affected by TGFbeta1 in BAECs. However, ATP-induced NO production was significantly reduced in TGFbeta1-treated BAECs. Anti-TGFbeta1 antibody abolished all of these TGFbeta1-induced changes in BAECs. CONCLUSIONS AND IMPLICATIONS: Mesenchymal transdifferentiation induced by TGFbeta1 leads to sustained contraction and reduced NO production in endothelial cells. Such effects, therefore, would not be beneficial for vascular integrity.
Mesh Headings (Keywords): Animals, Calcium, Cattle, Cell Differentiation, Cell Proliferation, Cell Shape, Cells, Cultured, Endothelial Cells, Microfilament Proteins, Muscle Cells, Muscle Contraction, Myosin Light Chains, Myosin-Light-Chain Phosphatase, Nitric Oxide, Phosphorylation, Time Factors, Transforming Growth Factor beta1
Check for Full Text / PubMed Unique Identifier (PMID): 16967050
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