© 1997 American Heart Association, Inc.
Articles |
Angiotensin II–Induced Stimulation of Smooth Muscle 
-Actin Expression by Serum Response Factor and the Homeodomain Transcription Factor MHox
From the Department of Molecular Physiology and Biological Physics (M.B.H., M.M.T., E.A.S., G.K.O.), University of Virginia Health Sciences Center, Charlottesville, and the Hamon Center for Basic Cancer Research (E.N.O.), The University of Texas Southwestern Medical Center, Dallas.
Correspondence to Dr Gary K. Owens, Department of Molecular Physiology and Biological Physics, Box 449, University of Virginia Health Sciences Center, Charlottesville, VA 22908. E-mail gko{at}virginia.edu
Abstract The objective of the present study was to
examine the molecular mechanisms whereby angiotensin II
(Ang II) stimulates smooth muscle (SM) -actin expression in rat
aortic smooth muscle cells (SMCs). Nuclear run-on analysis and
transfection studies indicated that the effects of Ang II on SM
-actin were mediated at least in part at the transcriptional level.
Transfection of various rat SM -actin promoter/chloramphenicol
acetyltransferase (CAT) constructs into SMCs demonstrated that the
first 155 bp of the SM -actin promoter was sufficient to confer
maximal Ang II responsiveness, conferring an 
4-fold increase in
reporter activities in these SMCs compared with vehicle-treated SMCs.
Mutation of either of two highly conserved CArG elements, designated A
(-62) and B (-112), completely abolished Ang II–induced increases in
reporter activity, whereas mutation of a homeodomain-like binding
sequence at -145 (ATTA) reduced reporter activity by half. Results of
EMSAs showed that nuclear extracts from Ang II–treated SMCs exhibited
enhanced binding activity of serum response factor (SRF) to the CArG
elements and of a homeo-domain factor, MHox, to the ATTA element.
Northern analyses showed that Ang II also stimulated marked
increases in MHox mRNA levels. Western analyses demonstrated
that Ang II–induced increases in SRF binding were not due to increased
SRF protein expression. Recombinant MHox markedly enhanced binding
activity of SRF in EMSAs. Finally, MHox overexpression
transactivated a SM -actin promoter/CAT reporter construct
by 3.5-fold in transient cotransfection studies. These results
provide evidence for involvement of a homeodomain transcription factor,
MHox, in Ang II–mediated stimulation of SM -actin via a
CArG/SRF-dependent mechanism.
Key Words: smooth muscle -actin promoter • vascular smooth muscle cell • angiotensin II • MHox
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