scholarly journals Smooth Muscle Differentiation Marker Gene Expression Is Regulated by RhoA-mediated Actin Polymerization

2000 ◽  
Vol 276 (1) ◽  
pp. 341-347 ◽  
Author(s):  
Christopher P. Mack ◽  
Avril V. Somlyo ◽  
Martina Hautmann ◽  
Andrew P. Somlyo ◽  
Gary K. Owens
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Actin Polymerization ◽  
Marker Gene ◽  
Muscle Differentiation ◽  
Marker Gene Expression ◽  
Smooth Muscle Differentiation ◽  
Differentiation Marker

scholarly journals Interleukin-1β modulates smooth muscle cell phenotype to a distinct inflammatory state relative to PDGF-DD via NF-κB-dependent mechanisms

2012 ◽  
Vol 44 (7) ◽  
pp. 417-429 ◽  
Author(s):  
Matthew R. Alexander ◽  
Meera Murgai ◽  
Christopher W. Moehle ◽  
Gary K. Owens
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Marker Gene ◽  
Marker Genes ◽  
Atherosclerotic Plaques ◽  
Phenotypic Modulation ◽  
Marker Gene Expression ◽  
Inflammatory State ◽  
Differentiation Marker

Smooth muscle cell (SMC) phenotypic modulation in atherosclerosis and in response to PDGF in vitro involves repression of differentiation marker genes and increases in SMC proliferation, migration, and matrix synthesis. However, SMCs within atherosclerotic plaques can also express a number of proinflammatory genes, and in cultured SMCs the inflammatory cytokine IL-1β represses SMC marker gene expression and induces inflammatory gene expression. Studies herein tested the hypothesis that IL-1β modulates SMC phenotype to a distinct inflammatory state relative to PDGF-DD. Genome-wide gene expression analysis of IL-1β- or PDGF-DD-treated SMCs revealed that although both stimuli repressed SMC differentiation marker gene expression, IL-1β distinctly induced expression of proinflammatory genes, while PDGF-DD primarily induced genes involved in cell proliferation. Promoters of inflammatory genes distinctly induced by IL-1β exhibited over-representation of NF-κB binding sites, and NF-κB inhibition in SMCs reduced IL-1β-induced upregulation of proinflammatory genes as well as repression of SMC differentiation marker genes. Interestingly, PDGF-DD-induced SMC marker gene repression was not NF-κB dependent. Finally, immunofluorescent staining of mouse atherosclerotic lesions revealed the presence of cells positive for the marker of an IL-1β-stimulated inflammatory SMC, chemokine (C-C motif) ligand 20 (CCL20), but not the PDGF-DD-induced gene, regulator of G protein signaling 17 (RGS17). Results demonstrate that IL-1β- but not PDGF-DD-induced phenotypic modulation of SMC is characterized by NF-κB-dependent activation of proinflammatory genes, suggesting the existence of a distinct inflammatory SMC phenotype. In addition, studies provide evidence for the possible utility of CCL20 and RGS17 as markers of inflammatory and proliferative state SMCs within atherosclerotic plaques in vivo.

GATA-6 mediates human bladder smooth muscle differentiation: involvement of a novel enhancer element in regulating α-smooth muscle actin gene expression

2007 ◽  
Vol 293 (3) ◽  
pp. C1093-C1102 ◽  
Author(s):  
Akihiro Kanematsu ◽  
Aruna Ramachandran ◽  
Rosalyn M. Adam
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Smooth Muscle Actin ◽  
Muscle Differentiation ◽  
Mrna Levels ◽  
Muscle Actin ◽  
Bladder Smooth Muscle ◽  
Human Bladder ◽  
Enhancer Element ◽  
Smooth Muscle Differentiation

Hollow organs exposed to pathological stimuli undergo phenotypic modulation characterized by altered expression of smooth muscle contractile proteins and loss of normal function. The molecular mechanisms that regulate smooth muscle differentiation, especially in organs other than the vasculature, are poorly understood. In this study, we describe a role for the GATA-6 transcription factor in regulation of human bladder smooth muscle differentiation. Knockdown of endogenous GATA-6 in primary human bladder smooth muscle cells (pBSMC) led to decreased mRNA levels of the differentiation markers α-smooth muscle actin (α-SMA), calponin, and smooth muscle myosin heavy chain. Similar effects were obtained following downregulation of GATA-6 by forskolin-induced elevation of intracellular cAMP levels. Forskolin treatment of pBSMC abolished recruitment of GATA-6 to the α-SMA promoter in vivo and reduced activity of human α-SMA promoter-directed gene expression by >60%. This inhibitory effect was rescued by enforced expression of wild-type GATA-6 but not by a zinc-finger-deleted mutant, GATA-6-ΔZF, which lacks DNA-binding ability. In silico analysis of a region of the human α-SMA promoter, described previously as a transcriptional enhancer, identified a putative GATA-binding site at position −919/−913. Point mutation of this site in SMA-Luc abrogated GATA-6-induced activation of promoter activity. Together, these results provide the first evidence for a functional role for GATA-6 in regulation of bladder smooth muscle differentiation. In addition, these findings demonstrate that GATA-6 regulates human α-SMA expression via a novel regulatory cis element in the α-SMA promoter-enhancer.

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