PMID- 17220908
OWN - NLM
STAT- MEDLINE
DCOM- 20070417
LR  - 20181113
IS  - 0007-1188 (Print)
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Linking)
VI  - 150
IP  - 4
DP  - 2007 Feb
TI  - Long-term treatment with TGFbeta1 impairs mechanotransduction in bovine aortic 
      endothelial cells.
PG  - 424-33
AB  - BACKGROUND AND PURPOSE: Vascular endothelial cells play a role in the 
      physiological response to mechanical stress. Transforming growth factor beta1 
      (TGFbeta1) induces morphological changes in endothelial cells, and this may alter 
      their mechanosensitive responses. The aim of this study was to examine the 
      effects of TGFbeta1 on hypotonic stress (HTS)-induced responses in bovine aortic 
      endothelial cells (BAECs). EXPERIMENTAL APPROACH: Cultured BAECs were treated 
      with 3 ng ml(-1) TGFbeta1 for 24 h (24h-TGFbeta1) or 7 days (7d-TGFbeta1). 
      Cytosolic actin fibres were stained with rhodamine-phalloidin. Intracellular Ca2+ 
      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 
      Ca2+ transients via endogenous ATP release in both control and 24h-TGFbeta1 BAECs 
      but not in 7d-TGFbeta1 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-TGFbeta1 than 
      in 24h-TGFbeta1 or control BAECs. HTS increased the membrane-bound RhoA to the 
      same fractional level in 24h-TGFbeta1 and control BAECs, but its net maximal 
      amount was significantly lower in 7d-TGFbeta1. HTS-induced downstream signals of 
      RhoA activation, i.e. the tyrosine phosphorylation of FAK and paxillin, were 
      markedly suppressed in 7d-TGFbeta1 BAECs. CONCLUSIONS AND IMPLICATIONS: These 
      results indicate that long-term treatment with TGFbeta1 does not impair 
      mechanoreception in BAECs but impairs mechanotransduction by affecting RhoA 
      membrane translocation.
FAU - Watanabe, M
AU  - Watanabe M
AD  - Department of Pharmacology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Oike, M
AU  - Oike M
FAU - Ohta, Y
AU  - Ohta Y
FAU - Ito, Y
AU  - Ito Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070115
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Actins)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Hypotonic Solutions)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 42HK56048U (Tyrosine)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
RN  - SY7Q814VUP (Calcium)
RN  - TSN3DL106G (Fura-2)
SB  - IM
MH  - Actins/physiology
MH  - Adenosine Triphosphate/metabolism/physiology
MH  - Animals
MH  - Aorta/cytology
MH  - Aorta, Thoracic/cytology/drug effects
MH  - Blotting, Western
MH  - Calcium/metabolism/physiology
MH  - Calcium Signaling/drug effects
MH  - Cattle
MH  - Cytosol/drug effects/ultrastructure
MH  - Endothelial Cells/*drug effects/ultrastructure
MH  - Fluorescent Dyes
MH  - Fura-2
MH  - Hypotonic Solutions
MH  - Mechanoreceptors/*drug effects
MH  - Phosphorylation
MH  - Physical Stimulation
MH  - RNA, Messenger/biosynthesis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/*drug effects
MH  - Transforming Growth Factor beta1/*pharmacology
MH  - Tyrosine/metabolism
MH  - rhoA GTP-Binding Protein/biosynthesis
PMC - PMC2189726
EDAT- 2007/01/16 09:00
MHDA- 2007/04/18 09:00
PMCR- 2008/02/01
CRDT- 2007/01/16 09:00
PHST- 2007/01/16 09:00 [pubmed]
PHST- 2007/04/18 09:00 [medline]
PHST- 2007/01/16 09:00 [entrez]
PHST- 2008/02/01 00:00 [pmc-release]
AID - 0707123 [pii]
AID - 10.1038/sj.bjp.0707123 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2007 Feb;150(4):424-33. doi: 10.1038/sj.bjp.0707123. Epub 2007 
      Jan 15.