© 1998 American Heart Association, Inc.
Original Contribution |
AML1-like Transcription Factor Induces Serine Elastase Activity in Ovine Pulmonary Artery Smooth Muscle Cells
From the Division of Cardiovascular Research, Research Institute, The Hospital for Sick Children, and the Departments of Pediatrics and Pathology, University of Toronto, Toronto, Ontario, Canada.
Abstract—In previous studies, we
showed that induction of pulmonary artery (PA) smooth muscle
cell (SMC) elastase activity by serum-treated elastin (STE)
requires DNA transcription. We therefore used differential mRNA display
to identify transcripts expressed coincident with elastase
induction. Twenty-four individual transcripts were differentially
expressed from a screen of 
2000 mRNA sequences. An mRNA with
sequence homology to the human transcription factor AML1 was identified
and subsequently cloned from ovine PA SMCs. Since AML1 binds to a
consensus sequence in the promoter of neutrophil elastase, we
pursued the possibility that AML1 is a candidate transcription factor
for SMC elastase. We documented by immunohistochemistry that serum
stimulation induces increased expression of AML1 in the nucleus of PA
SMCs. We also showed that STE induction of elastase activity is
associated with early expression of AML1 mRNA and protein and that AML1
consensus sequence DNA binding activity is increased in nuclear
extracts of STE-treated cells. In addition, AML1 antisense
oligonucleotides reduced serum induction
of elastase activity. Our study thus provides the first functional
evidence of AML1 transcriptional activity related to elastase genes
and offers novel insights into the broader biological significance of
AML1 in nonmyeloid cells.
Key Words: differential display polymerase chain reaction • pulmonary hypertension • AML1 transcription
This article has been cited by other articles:
 |
|
 |
|
  R. D. Bland, R. Ertsey, L. M. Mokres, L. Xu, B. E. Jacobson, S. Jiang, C. M. Alvira, M. Rabinovitch, E. S. Shinwell, and A. Dixit Mechanical ventilation uncouples synthesis and assembly of elastin and increases apoptosis in lungs of newborn mice.: Prelude to defective alveolar septation during lung development? Am J Physiol Lung Cell Mol Physiol, January 1, 2008; 294(1): L3 - L14. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rabinovitch The Mouse Through the Looking Glass: A New Door Into the Pathophysiology of Pulmonary Hypertension Circ. Res., April 30, 2004; 94(8): 1001 - 1004. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. MITANI, S. H. E. ZAIDI, P. DUFOURCQ, K. THOMPSON, and M. RABINOVITCH Nitric oxide reduces vascular smooth muscle cell elastase activity through cGMP-mediated suppression of ERK phosphorylation and AML1B nuclear partitioning FASEB J, April 1, 2000; 14(5): 805 - 814. [Abstract] [Full Text]
|
|
|
|
|
|
M. Rabinovitch EVE and beyond, retro and prospective insights Am J Physiol Lung Cell Mol Physiol, July 1, 1999; 277(1): L5 - L12. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. N. Cowan, P. L. Jones, and M. Rabinovitch Regression of Hypertrophied Rat Pulmonary Arteries in Organ Culture Is Associated With Suppression of Proteolytic Activity, Inhibition of Tenascin-C, and Smooth Muscle Cell Apoptosis Circ. Res., May 28, 1999; 84(10): 1223 - 1233. [Abstract] [Full Text] [PDF]
|
|