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c-Myb Regulates Proliferation and Differentiation of Adventitial Sca1+ Vascular Smooth Muscle Cell Progenitors by Transactivation of Myocardin.
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- Additional Information
- Source:
Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 9505803 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4636 (Electronic) Linking ISSN: 10795642 NLM ISO Abbreviation: Arterioscler Thromb Vasc Biol Subsets: MEDLINE
- Publication Information:
Publication: 1998- : Baltimore, Md. : Lippincott Williams & Wilkins
Original Publication: Dallas, TX : American Heart Association, c1995-
- Subject Terms:
Cell Differentiation*/
drug effects ;
Cell Proliferation*/
drug effects ;
Transcriptional Activation*;
Adventitia/
*metabolism ;
Ataxin-1/
*metabolism ;
Carotid Artery Injuries/
*metabolism ;
Muscle, Smooth, Vascular/
*metabolism ;
Myocytes, Smooth Muscle/
*metabolism ;
Nuclear Proteins/
*metabolism ;
Proto-Oncogene Proteins c-myb/
*metabolism ;
Stem Cells/
*metabolism ;
Trans-Activators/
*metabolism;
Adventitia/
drug effects ;
Adventitia/
injuries ;
Adventitia/
pathology ;
Animals ;
Binding Sites ;
Carotid Artery Injuries/
genetics ;
Carotid Artery Injuries/
pathology ;
Carotid Artery, Common/
metabolism ;
Carotid Artery, Common/
pathology ;
Disease Models, Animal ;
Genotype ;
HEK293 Cells ;
Humans ;
Mice, Inbred C57BL ;
Mice, Transgenic ;
Muscle, Smooth, Vascular/
drug effects ;
Muscle, Smooth, Vascular/
injuries ;
Muscle, Smooth, Vascular/
pathology ;
Myocytes, Smooth Muscle/
drug effects ;
Myocytes, Smooth Muscle/
pathology ;
Nuclear Proteins/
genetics ;
Phenotype ;
Promoter Regions, Genetic ;
Proto-Oncogene Proteins c-myb/
genetics ;
Signal Transduction ;
Stem Cells/
drug effects ;
Stem Cells/
pathology ;
Time Factors ;
Trans-Activators/
genetics ;
Transcription, Genetic ;
Transfection ;
Transforming Growth Factor beta1/
pharmacology ;
Vascular Remodeling - Abstract:
Objective: Vascular smooth muscle cells (VSMCs) are believed to dedifferentiate and proliferate in response to vessel injury. Recently, adventitial progenitor cells were implicated as a source of VSMCs involved in vessel remodeling. c-Myb is a transcription factor known to regulate VSMC proliferation in vivo and differentiation of VSMCs from mouse embryonic stem cell-derived progenitors in vitro. However, the role of c-Myb in regulating specific adult vascular progenitor cell populations was not known. Our objective was to examine the role of c-Myb in the proliferation and differentiation of Sca1(+) adventitial VSMC progenitor cells.
Approach and Results: Using mice with wild-type or hypomorphic c-myb (c-myb(h/h)), BrdU (bromodeoxyuridine) uptake and flow cytometry revealed defective proliferation of Sca1(+) adventitial VSMC progenitor cells at 8, 14, and 28 days post carotid artery denudation injury in c-myb(h/h) arteries. c-myb(h/h) cKit(+)CD34(-)Flk1(-)Sca1(+)CD45(-)Lin(-) cells failed to proliferate, suggesting that c-myb regulates the activation of specific Sca1(+) progenitor cells in vivo and in vitro. Although expression levels of transforming growth factor-β1 did not vary between wild-type and c-myb(h/h) carotid arteries, in vitro differentiation of c-myb(h/h) Sca1(+) cells manifested defective transforming growth factor-β1-induced VSMC differentiation. This is mediated by reduced transcriptional activation of myocardin because chromatin immunoprecipitation revealed c-Myb binding to the myocardin promoter only during differentiation of Sca1(+) cells, myocardin promoter mutagenesis identified 2 specific c-Myb-responsive binding sites, and adenovirus-mediated expression of myocardin rescued the phenotype of c-myb(h/h) progenitors.
Conclusions: These data support a role for c-Myb in the regulation of VSMC progenitor cells and provide novel insight into how c-myb regulates VSMC differentiation through myocardin.
(© 2016 American Heart Association, Inc.)
- Grant Information:
MOP-136850 Canada CIHR
- Contributed Indexing:
Keywords: c-Myb genes; cell differentiation; myocardin; progenitor cells; smooth muscle cells
- Accession Number:
0 (Ataxin-1)
0 (Atxn1 protein, mouse)
0 (Nuclear Proteins)
0 (Proto-Oncogene Proteins c-myb)
0 (Trans-Activators)
0 (Transforming Growth Factor beta1)
0 (myocardin)
- Publication Date:
Date Created: 20160514 Date Completed: 20170619 Latest Revision: 20180521
- Publication Date:
20221213
- Accession Number:
10.1161/ATVBAHA.115.307116
- Accession Number:
27174098
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