Gene Expression Profiling of Leiomyoma and Myometrial Smooth Muscle Cells in Response to Transforming Growth Factor-β

Altered expression of the TGF-β system is recognized to play a central role in various fibrotic disorders, including leiomyoma. In this study we performed microarray analysis to characterize the gene expression profile of leiomyoma and matched myometrial smooth muscle cells (LSMC and MSMC, respectively) in response to the time-dependent action of TGF-β and, after pretreatment with TGF-β type II receptor (TGF-βRII) antisense oligomer-blocking/reducing TGF-β autocrine/paracrine actions. Unsupervised and supervised assessments of the gene expression values with a false discovery rate selected at P ≤ 0.001 identified 310 genes as differentially expressed and regulated in LSMC and MSMC in a cell- and time-dependent manner by TGF-β. Pretreatment with TGF-βRII antisense resulted in changes in the expression of many of the 310 genes regulated by TGF-β, with 54 genes displaying a response to TGF-β treatment. Comparative analysis of the gene expression profile in TGF-βRII antisense- and GnRH analog-treated cells indicated that these treatments target the expression of 222 genes in a cell-specific manner. Gene ontology assigned these genes functions as cell cycle regulators, transcription factors, signal transducers, tissue turnover, and apoptosis. We validated the expression and TGF-β time-dependent regulation of IL-11, TGF-β-induced factor, TGF-β-inducible early gene response, early growth response 3, CITED2 (cAMP response element binding protein-binding protein/p300-interacting transactivator with ED-rich tail), Nur77, Runx1, Runx2, p27, p57, growth arrest-specific 1, and G protein-coupled receptor kinase 5 in LSMC and MSMC using real-time PCR. Together, the results provide the first comprehensive assessment of the LSMC and MSMC molecular environment targeted by autocrine/paracrine action of TGF-β, highlighting potential involvement of specific genes whose products may influence the outcome of leiomyoma growth and fibrotic characteristics by regulating inflammatory response, cell growth, apoptosis, and tissue remodeling.

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IL-17A Mediates a Selective Gene Expression Profile in Asthmatic Human Airway Smooth Muscle Cells

American Journal of Respiratory Cell and Molecular Biology ◽

10.1165/rcmb.2012-0267oc ◽

2014 ◽

Vol 50 (6) ◽

pp. 1053-1063 ◽

Cited By ~ 13

Author(s):

Stéphane Dragon ◽

Stuart J. Hirst ◽

Tak H. Lee ◽

Abdelilah S. Gounni

Keyword(s):

Gene Expression ◽

Smooth Muscle ◽

Smooth Muscle Cells ◽

Gene Expression Profile ◽

Airway Smooth Muscle ◽

Expression Profile ◽

Muscle Cells ◽

Airway Smooth Muscle Cells ◽

Human Airway Smooth Muscle ◽

Human Airway

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330 EARLY CHANGES IN VASCULAR SMOOTH MUSCLE CELLS GENE EXPRESSION PROFILE IN RESPONSE TO VASCULAR INJURY

Atherosclerosis Supplements ◽

10.1016/s1567-5688(11)70331-2 ◽

2011 ◽

Vol 12 (1) ◽

pp. 71

Author(s):

A. Fedorov ◽

A. Razuvaev ◽

A. Kostareva ◽

U. Hedin ◽

J. Raud ◽

...

Keyword(s):

Gene Expression ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Gene Expression Profile ◽

Vascular Smooth Muscle Cells ◽

Vascular Injury ◽

Expression Profile ◽

Muscle Cells

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Gene expression profile of the Gs-coupled prostacyclin receptor in human vascular smooth muscle cells

Biochemical Pharmacology ◽

10.1016/j.bcp.2003.07.022 ◽

2004 ◽

Vol 67 (4) ◽

pp. 757-765 ◽

Cited By ~ 22

Author(s):

Jutta Meyer-Kirchrath ◽

Svenja Debey ◽

Christian Glandorff ◽

Lutz Kirchrath ◽

Karsten Schrör

Keyword(s):

Gene Expression ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Gene Expression Profile ◽

Vascular Smooth Muscle Cells ◽

Expression Profile ◽

Muscle Cells ◽

Prostacyclin Receptor

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Na+/H+ exchange isoform-1 gene expression induced by aldosterne is regulated through CCAAT/enhancer binding protein δ in vascular smooth muscle cells

American Journal of Hypertension ◽

10.1016/j.amjhyper.2005.03.708 ◽

2005 ◽

Vol 18 (5) ◽

pp. A260-A261

Author(s):

J IRITA ◽

T FUKUOKA ◽

S MANABE ◽

M KURATA ◽

K MIYOSHI ◽

...

Keyword(s):

Gene Expression ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Binding Protein ◽

Muscle Cells ◽

Enhancer Binding Protein ◽

Ccaat Enhancer Binding Protein

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Immediate early gene expression in vascular smooth-muscle cells synergistically induced by hemolysate components

Journal of Neurosurgery ◽

10.3171/jns.1999.90.6.1083 ◽

1999 ◽

Vol 90 (6) ◽

pp. 1083-1090 ◽

Cited By ~ 22

Author(s):

Xiaoyu Wang ◽

Linda S. Marton ◽

Bryce K. A. Weir ◽

R. Loch Macdonald

Keyword(s):

Gene Expression ◽

Smooth Muscle ◽

Smooth Muscle Cells ◽

Synergistic Effects ◽

Muscle Cells ◽

Immediate Early Gene ◽

Early Gene ◽

Immediate Early ◽

Content Type ◽

Fine Print

Object. Vasospasm after subarachnoid hemorrhage is associated with changes in modulators of vascular tone in the arterial wall and is related to the presence of erythrocyte hemolysate in the subarachnoid space. The purpose of this study was to determine the compounds in erythrocyte hemolysate that are responsible for changing smooth-muscle cell gene expression.Methods. Rat aorta smooth-muscle cells were exposed to erythrocyte hemolysate in vitro and the effects on immediate early gene messenger (m)RNA levels were determined by competitive reverse transcriptase—polymerase chain reaction.Message levels for c-fos, jun B, and c-jun were increased in the presence of hemolysate, reaching maximum expression between 30 and 60 minutes, whereas the level of jun D mRNA was unaffected. Increasing doses of hemolysate caused greater expression of c-fos and jun B, but not c-jun. Adenosine triphosphate and hemoglobin, possible spasmogens present in hemolysate, caused much smaller and more rapid increases in c-fos expression than whole hemolysate. Size fractionation showed that all of the c-fos mRNA—inducing activity of hemolysate was recovered with molecules greater than 6 kD. Following separation of hemolysate proteins by hydrophobic interaction chromatography, only one of the three fractions had partial activity. Recombining the three fractions, however, yielded greater c-fos activation than any combination of two.Conclusions. Multiple high-molecular-weight components present in erythrocytes have synergistic effects on gene expression in smooth-muscle cells. The differences in patterns of gene induction suggest that multiple signaling pathways are activated.

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Immediate-early gene expression in response to hypertrophic and proliferative stimuli in pulmonary arterial smooth muscle cells.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)37385-4 ◽

1994 ◽

Vol 269 (9) ◽

pp. 6399-6404

Author(s):

A. Rothman ◽

B. Wolner ◽

D. Button ◽

P. Taylor

Keyword(s):

Gene Expression ◽

Smooth Muscle ◽

Smooth Muscle Cells ◽

Muscle Cells ◽

Early Gene ◽

Immediate Early ◽

Early Gene Expression ◽

Pulmonary Arterial ◽

Arterial Smooth Muscle Cells ◽

Pulmonary Arterial Smooth Muscle

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Extracellular acidosis induces heme oxygenase-1 expression in vascular smooth muscle cells

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00937.2004 ◽

2005 ◽

Vol 288 (6) ◽

pp. H2647-H2652 ◽

Cited By ~ 16

Author(s):

Helen Christou ◽

Nicole Bailey ◽

Morgan S. Kluger ◽

S. Alex Mitsialis ◽

Stella Kourembanas

Keyword(s):

Gene Expression ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Heme Oxygenase ◽

Vascular Tone ◽

Muscle Cells ◽

Time Dependent ◽

Extracellular Acidosis

Extracellular acidosis (EA) has profound effects on vascular homeostasis, including vascular bed-specific alterations in vascular tone. Regulation of gene expression by EA has been observed in a variety of cells including vascular endothelial cells. Whether EA regulates gene expression in vascular smooth muscle cells (VSMCs) is not known. Heme oxygenase (HO)-1 is expressed in vascular cells, and its expression is regulated by cellular stressors such as heat, radiation, and hypoxia. Increased HO-1 expression in VSMCs leads to increased production of CO and its second messenger cGMP, which are important regulators of vascular tone and paracrine interactions in the vasculature. We examined whether EA regulates the expression of HO-1 in VSMCs. Exposure of VSMCs to acidic medium (pH 6.8) significantly increased HO-1 mRNA and protein compared with exposure to medium of physiological pH (pH 7.4). The acidic induction of HO-1 expression was time dependent and involved both transcriptional activation of the HO-1 gene and enhanced stability of HO-1 mRNA. Nitric oxide did not appear to mediate this response. We conclude that HO-1 is transcriptionally and posttranscriptionally upregulated by EA in VSMCs. This induction is time dependent and reversible. We speculate that EA, as an important tissue and cellular stressor for VSMCs, may elicit changes in gene expression patterns that contribute to the maintenance or disruption of vascular homeostasis.

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