Forced expression of myocardin is not sufficient for induction of smooth muscle differentiation in multipotential embryonic cells

Tadashi Yoshida, Keiko Kawai-Kowase, Gary K. Owens

研究成果: Article

77 引用 (Scopus)

抄録

Objective-Myocardin, a coactivator of serum response factor, has been shown to be required for expression of multiple CArG-dependent smooth muscle cell (SMC) marker genes. The aim of the present study was to determine whether myocardin alone is sufficient to induce SMC lineage in multipotential stem cells as evidenced by activation of the entire SMC differentiation program. Methods and Results-Overexpression of myocardin induced only a subset of SMC marker genes, including smooth muscle (SM) α-actin, SM-myosin heavy chain (MHC), SM22α, calponin, and desmin in A404 SMC precursor cells, whereas expression of smoothelin-B, aortic carboxypeptidase-like protein, and focal adhesion kinase-related nonkinase, whose promoters lack efficacious CArG elements, was not induced. Similar results were obtained in cultured SMCs, 10T1/2 cells, and embryonic stem cells. Moreover, myocardin inappropriately induced expression of skeletal and cardiac CArG-dependent genes in cultured SMCs. Stable overexpression of dominant-negative myocardin in A404 cells resulted in impaired induction of SM α-actin and SM-MHC by all trans-retinoic acid but had no effect on induction of smoothelin-B and aortic carboxypeptidase-like protein expression. Conclusions-Taken together with previous studies, results demonstrate that myocardin is required for the induction of CArG-dependent SMC marker genes but is not sufficient to initiate the complete SMC differentiation program.

元の言語English
ページ(範囲)1596-1601
ページ数6
ジャーナルArteriosclerosis, Thrombosis, and Vascular Biology
24
発行部数9
DOI
出版物ステータスPublished - 2004 9
外部発表Yes

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Smooth Muscle Myocytes
Smooth Muscle
Carboxypeptidase B
Smooth Muscle Myosins
Myosin Heavy Chains
Genes
Actins
Cell Differentiation
Serum Response Factor
Focal Adhesion Protein-Tyrosine Kinases
Desmin
Cell Lineage
Embryonic Stem Cells
Tretinoin
myocardin
Proteins
Stem Cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

これを引用

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abstract = "Objective-Myocardin, a coactivator of serum response factor, has been shown to be required for expression of multiple CArG-dependent smooth muscle cell (SMC) marker genes. The aim of the present study was to determine whether myocardin alone is sufficient to induce SMC lineage in multipotential stem cells as evidenced by activation of the entire SMC differentiation program. Methods and Results-Overexpression of myocardin induced only a subset of SMC marker genes, including smooth muscle (SM) α-actin, SM-myosin heavy chain (MHC), SM22α, calponin, and desmin in A404 SMC precursor cells, whereas expression of smoothelin-B, aortic carboxypeptidase-like protein, and focal adhesion kinase-related nonkinase, whose promoters lack efficacious CArG elements, was not induced. Similar results were obtained in cultured SMCs, 10T1/2 cells, and embryonic stem cells. Moreover, myocardin inappropriately induced expression of skeletal and cardiac CArG-dependent genes in cultured SMCs. Stable overexpression of dominant-negative myocardin in A404 cells resulted in impaired induction of SM α-actin and SM-MHC by all trans-retinoic acid but had no effect on induction of smoothelin-B and aortic carboxypeptidase-like protein expression. Conclusions-Taken together with previous studies, results demonstrate that myocardin is required for the induction of CArG-dependent SMC marker genes but is not sufficient to initiate the complete SMC differentiation program.",
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AU - Yoshida, Tadashi

AU - Kawai-Kowase, Keiko

AU - Owens, Gary K.

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N2 - Objective-Myocardin, a coactivator of serum response factor, has been shown to be required for expression of multiple CArG-dependent smooth muscle cell (SMC) marker genes. The aim of the present study was to determine whether myocardin alone is sufficient to induce SMC lineage in multipotential stem cells as evidenced by activation of the entire SMC differentiation program. Methods and Results-Overexpression of myocardin induced only a subset of SMC marker genes, including smooth muscle (SM) α-actin, SM-myosin heavy chain (MHC), SM22α, calponin, and desmin in A404 SMC precursor cells, whereas expression of smoothelin-B, aortic carboxypeptidase-like protein, and focal adhesion kinase-related nonkinase, whose promoters lack efficacious CArG elements, was not induced. Similar results were obtained in cultured SMCs, 10T1/2 cells, and embryonic stem cells. Moreover, myocardin inappropriately induced expression of skeletal and cardiac CArG-dependent genes in cultured SMCs. Stable overexpression of dominant-negative myocardin in A404 cells resulted in impaired induction of SM α-actin and SM-MHC by all trans-retinoic acid but had no effect on induction of smoothelin-B and aortic carboxypeptidase-like protein expression. Conclusions-Taken together with previous studies, results demonstrate that myocardin is required for the induction of CArG-dependent SMC marker genes but is not sufficient to initiate the complete SMC differentiation program.

AB - Objective-Myocardin, a coactivator of serum response factor, has been shown to be required for expression of multiple CArG-dependent smooth muscle cell (SMC) marker genes. The aim of the present study was to determine whether myocardin alone is sufficient to induce SMC lineage in multipotential stem cells as evidenced by activation of the entire SMC differentiation program. Methods and Results-Overexpression of myocardin induced only a subset of SMC marker genes, including smooth muscle (SM) α-actin, SM-myosin heavy chain (MHC), SM22α, calponin, and desmin in A404 SMC precursor cells, whereas expression of smoothelin-B, aortic carboxypeptidase-like protein, and focal adhesion kinase-related nonkinase, whose promoters lack efficacious CArG elements, was not induced. Similar results were obtained in cultured SMCs, 10T1/2 cells, and embryonic stem cells. Moreover, myocardin inappropriately induced expression of skeletal and cardiac CArG-dependent genes in cultured SMCs. Stable overexpression of dominant-negative myocardin in A404 cells resulted in impaired induction of SM α-actin and SM-MHC by all trans-retinoic acid but had no effect on induction of smoothelin-B and aortic carboxypeptidase-like protein expression. Conclusions-Taken together with previous studies, results demonstrate that myocardin is required for the induction of CArG-dependent SMC marker genes but is not sufficient to initiate the complete SMC differentiation program.

KW - CArG element

KW - Serum response factor

KW - Smooth muscle cells

KW - Transcriptional coactivator

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