Long-term treatment with TGFβ 1 impairs mechanotransduction in bovine aortic endothelial cells

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

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Background and purpose: Vascular endothelial cells play a role in the physiological response to mechanical stress. Transforming growth factor β 1 (TGFβ 1) induces morphological changes in endothelial cells, and this may alter their mechanosensitive responses. The aim of this study was to examine the effects of TGFβ 1 on hypotonic stress (HTS)-induced responses in bovine aortic endothelial cells (BAECs). Experimental approach: Cultured BAECs were treated with 3 ng ml -1 TGFβ 1 for 24 h (24h-TGFβ 1) or 7 days (7d-TGFβ 1). Cytosolic actin fibres were stained with rhodamine-phalloidin. Intracellular Ca 2+ concentration was measured using fura2. Tyrosine phosphorylation and RhoA expression were assessed by Western blotting. Expression of RhoA mRNA was assessed by real-time PCR. Key results: BAECs developed pseudopod-like processes within 24 h and showed a fibroblast-like appearance after 7 days. HTS induced Ca 2+ transients via endogenous ATP release in both control and 24h-TGFβ 1 BAECs but not in 7d-TGFβ 1 BAECs. We have previously shown that HTS-induced ATP release is mediated by sequential activation of RhoA and tyrosine kinases. The basal amount of membrane-bound RhoA was significantly lower in 7d-TGFβ 1 than in 24h-TGFβ 1 or control BAECs. HTS increased the membrane-bound RhoA to the same fractional level in 24h-TGFβ 1 and control BAECs, but its net maximal amount was significantly lower in 7d-TGFβ 1. HTS-induced downstream signals of RhoA activation, i.e. the tyrosine phosphorylation of FAK and paxillin, were markedly suppressed in 7d-TGFβ 1 BAECs. Conclusions and Implications: These results indicate that long-term treatment with TGFβ 1 does not impair mechanoreception in BAECs but impairs mechanotransduction by affecting RhoA membrane translocation.

Original languageEnglish
Pages (from-to)424-433
Number of pages10
JournalBritish Journal of Pharmacology
Volume150
Issue number4
DOIs
Publication statusPublished - Feb 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology

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