Actin expression in smooth muscle cells of rat aortic intimal thickening, human atheromatous plaque, and cultured rat aortic media.

Gabbiani, Giulio; Kocher, Olivier; Bloom, William; Vandekerckhove, Joël; Weber, Klaus

doi:10.1172/jci111185

Cited by 324 publications

(131 citation statements)

References 25 publications

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“…Differentiated smooth muscle cells are characterized by their expression of a unique subset of contractile protein isoforms including smooth muscle ␣-actin (15)(16)(17)(18), smooth muscle ␥-actin (17)(18)(19)(20)(21), smooth muscle myosin heavy and light chains (22)(23)(24), calponin (25), SM22␣ (26 -28), and telokin (29 -31). Furthermore, these cells possess the capability to express appropriate levels of these characteristic smooth muscle proteins even though they are derived from diverse embryonic origins (32).…”

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confidence: 99%

The Smooth Muscle γ-Actin Gene Promoter Is a Molecular Target for the Mouse bagpipe Homologue, mNkx3-1, and Serum Response Factor

Carson¹,

Fillmore²,

Schwartz³

et al. 2000

Journal of Biological Chemistry

104

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An evolutionarily conserved vertebrate homologue of the Drosophila NK-3 homeodomain gene bagpipe, Nkx3-1, is expressed in vascular and visceral mesodermderived muscle tissues and may influence smooth muscle cell differentiation. Nkx3-1 was evaluated for mediating smooth muscle ␥-actin (SMGA) gene activity, a specific marker of smooth muscle differentiation. Expression of mNkx3-1 in heterologous CV-1 fibroblasts was unable to elicit SMGA promoter activity but required the coexpression of serum response factor (SRF) to activate robust SMGA transcription. A novel complex element containing a juxtaposed Nkx-binding site (NKE) and an SRF-binding element (SRE) in the proximal promoter region was found to be necessary for the Nkx3-1/ SRF coactivation of SMGA transcription. Furthermore, Nkx3-1 and SRF associate through protein-protein interactions and the homeodomain region of Nkx3-1 facilitated SRF binding to the complex NKE⅐SRE. Mutagenesis of Nkx3-1 revealed an inhibitory domain within its C-terminal segment. In addition, mNkx3-1/SRF cooperative activity required an intact Nkx3-1 homeodomain along with the MADS box of SRF, which contains DNA binding and dimerization structural domains, and the contiguous C-terminal SRF activation domain. Thus, SMGA is a novel target for Nkx3-1, and the activity of Nkx3-1 on the SMGA promoter is dependent upon SRF.

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confidence: 99%

The Smooth Muscle γ-Actin Gene Promoter Is a Molecular Target for the Mouse bagpipe Homologue, mNkx3-1, and Serum Response Factor

Carson¹,

Fillmore²,

Schwartz³

et al. 2000

Journal of Biological Chemistry

104

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“…These differentiated, contractile smooth muscle cells are characterized by the presence of unique isoforms of contractile proteins such as smooth muscle ␣-and ␥-actin, myosin heavy chain, caldesmon, calponin, SM22␣, and telokin (4, 9 -16). In vitro culture of smooth muscle cells, in the presence of high levels of serum, results in a marked decrease in the expression of many smooth muscle contractile proteins, including smooth muscle myosin, smooth muscle actin, h-caldesmon, calponin, smooth muscle myosin light chain kinase, and telokin with a concomitant increase in the expression of non-muscle contractile protein isoforms (2,14,(17)(18)(19). 1 A similar increase in nonmuscle myosin has been reported in smooth muscle cells during restenosis (20,21).…”

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confidence: 99%

Targeted Expression of SV40 Large T-antigen to Visceral Smooth Muscle Induces Proliferation of Contractile Smooth Muscle Cells and Results in Megacolon

Herring

Hoggatt

Smith

et al. 1999

Journal of Biological Chemistry

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Many pathological conditions result from the proliferation and de-differentiation of smooth muscle cells leading to impaired contractility of the muscle. Here we show that targeted expression of SV40 large T-antigen to visceral smooth muscle cells in vivo results in increased smooth muscle cell proliferation without de-differentiation or decreased contractility. These data suggest that the de-differentiation and proliferation of smooth muscle cells, seen in many pathological states, may be independently regulated. In the T-antigen transgenic mice the increased smooth muscle cell proliferation results in thickening of the distal colon. Consequently the distal colon becomes hyper-contractile and impedes the flow of digesta through the colon resulting in enlargement of the colon oral to the obstruction. These transgenic mice thus represent a novel model of megacolon that results from increased smooth muscle cell proliferation rather than altered neuronal innervation.Under many pathological conditions smooth muscle cells undergo phenotypic modulation in which they change from a contractile quiescent phenotype to a synthetic proliferative state. The phenotypic changes observed depend on the severity of the injury and the specific smooth muscle tissue involved (1-8). Smooth muscle cells in adult tissues are normally quiescent, exhibit very low rates of division, and express high levels of contractile proteins and myofilaments. These differentiated, contractile smooth muscle cells are characterized by the presence of unique isoforms of contractile proteins such as smooth muscle ␣-and ␥-actin, myosin heavy chain, caldesmon, calponin, SM22␣, and telokin (4, 9 -16). In vitro culture of smooth muscle cells, in the presence of high levels of serum, results in a marked decrease in the expression of many smooth muscle contractile proteins, including smooth muscle myosin, smooth muscle actin, h-caldesmon, calponin, smooth muscle myosin light chain kinase, and telokin with a concomitant increase in the expression of non-muscle contractile protein isoforms (2,14,(17)(18)(19).1 A similar increase in nonmuscle myosin has been reported in smooth muscle cells during restenosis (20,21). In contrast, in intimal cells from human coronary arteries, it has been reported that there is reduced expression of SM2 smooth muscle myosin heavy chain without any detectable increase in non-muscle myosin heavy chain B (5). These examples illustrate that smooth muscle cells can exhibit a plethora of phenotypes ranging from fully differentiated quiescent contractile cells to cells expressing low levels of contractile proteins and proliferating rapidly (22).In most in vivo models of vascular, airway, and intestinal injury, smooth muscle cells are subject to mechanical and/or cytological trauma resulting in exposure to growth factors and re-entry into the cell cycle. Together these agents increase smooth muscle cell proliferation and cause phenotypic modulation altering the contractile properties of the muscle (22, 23). As both proliferation and phenot...

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“…This may be due to an exogenous or endogenous stimulus affecting a single (or few) cell(s) but may also depend on the fact that SMCs are heterogeneous in their replicative potentiality. It has also been shown that human and experimental atheromatous SMCs show dedifferentiated features, at least as far as their morphology (for review see Reference 5) and cytoskeletal equipment 6 " 9 are concerned, and the above considerations may apply to the acquisition of such features by SMCs. The possible heterogeneity of SMCs has been little explored until now because of the lack of experimental models.…”

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confidence: 99%

Age influences the replicative activity and the differentiation features of cultured rat aortic smooth muscle cell populations and clones.

Bochaton‐Piallat

Gabbiani

Ropraz

et al. 1993

Arterioscler Thromb

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The replicative activity and the differentiation features of aortic smooth muscle cells (SMCs) cultured as whole populations or clones from newborn (4-day-old), young adult (6-week-old), and old (18-month-old) rats were studied by means of cell counting, [3 H]thymidine incorporation, and measurement of the expression of cytoskeletal proteins and mRNAs. In whole populations at the fifth passage, replicative activity increased and differentiation features (ie, expression of o-smooth muscle actin, desmin, and smooth muscle myosin heavy chains) decreased with increasing age of the donor animal. SMC clones derived from newborn or young adult rats showed more differentiated cytoskeletal features than their parental populations; however, most SMC clones from old rats showed differentiated features similar to those observed in their parental populations. Our results suggest that (1) SMCs of the rat aortic media behave as a heterogeneous population; (2) cultured whole SMC populations behave differently from clones as far as their replicative activity and differentiation features are concerned; and (3) SMCs derived from old rats, whether grown as whole populations or as clones, dedifferentiate more substantially and replicate more actively than corresponding cultures from newborn or young adult rats when submitted to the same amount of serum growth factors; these differences may play a role in arterial development as well as in the formation and evolution of the atheromatous plaque. O ne of the major features of atheromatous plaque development is the increase of the intimal cell population, which is mainly due to medial smooth muscle cell (SMC) migration and proliferation (for review see References 1 to 3). The early observations of Benditt and Benditt 4 suggest that the initial SMC proliferative event must involve a small proportion of the media population, possibly one cell. This may be due to an exogenous or endogenous stimulus affecting a single (or few) cell(s) but may also depend on the fact that SMCs are heterogeneous in their replicative potentiality. It has also been shown that human and experimental atheromatous SMCs show dedifferentiated features, at least as far as their morphology (for review see Reference 5) and cytoskeletal equipment 6 " 9 are concerned, and the above considerations may apply to the acquisition of such features by SMCs. The possible heterogeneity of SMCs has been little explored until now because of the lack of experimental models. A suitable model could be based on the production of SMC clones. Ideally, these clones should be produced from human SMCs; practically, however, clones derived from SMCs of an experimental animal are relatively easy to obtain and may furnish new, useful information on the general biology of arterial SMCs.Received March 30, 1993; revision accepted June 16, 1993. From the Department of Pathology, University of Geneva, Geneva, Switzerland.Correspondence to G. Gabbiani, Department of Pathology, University of Geneva, CMU, 1 Rue Michel Servet, 1211 Geneva 4, Switzerlan...

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Actin expression in smooth muscle cells of rat aortic intimal thickening, human atheromatous plaque, and cultured rat aortic media.

Cited by 324 publications

References 25 publications

The Smooth Muscle γ-Actin Gene Promoter Is a Molecular Target for the Mouse bagpipe Homologue, mNkx3-1, and Serum Response Factor

The Smooth Muscle γ-Actin Gene Promoter Is a Molecular Target for the Mouse bagpipe Homologue, mNkx3-1, and Serum Response Factor

Targeted Expression of SV40 Large T-antigen to Visceral Smooth Muscle Induces Proliferation of Contractile Smooth Muscle Cells and Results in Megacolon

Age influences the replicative activity and the differentiation features of cultured rat aortic smooth muscle cell populations and clones.

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