Sustained contraction and loss of NO production in TGFβ 1- treated endothelial cells

M. Watanabe, M. Oike, Y. Ohta, H. Nawata, Y. Ito

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8 Citations (Scopus)

Abstract

Background and purpose: Transforming growth factor β 1 (TGFβ 1) is generated in atherosclerotic and injured vessel walls. We examined whether the endothelial-to-mesenchymal transdifferentiation induced by TGFβ 1 affects endothelial functions. Experimental approach: Bovine aortic endothelial cells (BAECs) were treated with 3 ng ml -1 TGFβ 1 for 7 days. Contraction of TGFβ 1-treated BAECs was assessed by collagen gel contraction assay. Protein expression and phosphorylation were assessed by Western blotting. Intracellular Ca 2+ concentration and NO production were measured using fura2 and DAF-2, respectively. Key results: TGFβ 1-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 μM) induced a gradual contraction of collagen gels containing TGFβ 1-treated BAECs but not of gels containing control BAECs. ATP-induced contraction of TGFβ 1-treated BAECs was not reversed by the removal of ATP but was partially suppressed by a high concentration of sodium nitroprusside (1μM). TGFβ 1-treated BAECs showed sustained phosphorylation of myosin light chain in response to ATP and low levels of basal MYPT1 expression. ATP-induced Ca 2+ transients as well as eNOS protein expression were not affected by TGFβ 1 in BAECs. However, ATP-induced NO production was significantly reduced in TGFβ 1-treated BAECs. Anti-TGFβ 1 antibody abolished all of these TGFβ 1-induced changes in BAECs.Conclusions and Implications:Mesenchymal transdifferentiation induced by TGFβ 1 leads to sustained contraction and reduced NO production in endothelial cells. Such effects, therefore, would not be beneficial for vascular integrity.

Original languageEnglish
Pages (from-to)355-364
Number of pages10
JournalBritish Journal of Pharmacology
Volume149
Issue number4
DOIs
Publication statusPublished - Oct 11 2006

All Science Journal Classification (ASJC) codes

  • Pharmacology

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