Document Detail

Mechanisms of TGF-β-induced differentiation in human vascular smooth muscle cells.
MedLine Citation:
PMID:  21832838     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Transforming growth factor-β (TGF-β) plays an important role in vascular homeostasis through effects on vascular smooth muscle cells (SMC). Fine-tuning of TGF-β signaling occurs at the level of ALK receptors or Smads, and is regulated with cell type specificity.
METHODS: Our goal was to understand TGF-β signaling in regulating SMC differentiation marker expression in human SMC. Activation of Smads was characterized, and loss- and gain-of-function reagents used to define ALK pathways. In addition, Smad-independent mechanisms were determined.
RESULTS: TGF-β type I receptors, ALK1 and ALK5, are expressed in human SMC, and TGF-β1 phosphorylates Smad1/5/8 and Smad2/3 in a time- and dosage-dependent pattern. ALK5 activity, not bone morphogenetic protein type I receptors, is required for Smad phosphorylation. Endoglin, a TGF-β type III receptor, is a TGF-β1 target in SMC, yet endoglin does not modify TGF-β1 responsiveness. ALK5, not ALK1, is required for TGF-β1-induction of SMC differentiation markers, and ALK5 signals through an ALK5/Smad3- and MAP kinase-dependent pathway.
CONCLUSION: The definition of the specific signaling downstream of TGF-β regulating SMC differentiation markers will contribute to a better understanding of vascular disorders involving changes in SMC phenotype.
Yuefeng Tang; Xuehui Yang; Robert E Friesel; Calvin P H Vary; Lucy Liaw
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-08-11
Journal Detail:
Title:  Journal of vascular research     Volume:  48     ISSN:  1423-0135     ISO Abbreviation:  J. Vasc. Res.     Publication Date:  2011  
Date Detail:
Created Date:  2011-10-11     Completed Date:  2011-12-06     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  9206092     Medline TA:  J Vasc Res     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  485-94     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 S. Karger AG, Basel.
Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074, USA.
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MeSH Terms
Activin Receptors, Type II / metabolism
Antigens, CD / genetics,  metabolism
Aorta / cytology
Bone Morphogenetic Protein Receptors, Type I / metabolism
Cell Differentiation / drug effects,  physiology
Cells, Cultured
Gene Expression / physiology
Muscle, Smooth, Vascular / cytology*,  drug effects,  metabolism*
Phosphorylation / drug effects,  physiology
Protein-Serine-Threonine Kinases / metabolism
Receptors, Cell Surface / genetics,  metabolism
Receptors, Transforming Growth Factor beta / metabolism
Signal Transduction / drug effects,  physiology*
Smad1 Protein / metabolism
Smad2 Protein / metabolism
Smad3 Protein / metabolism
Smad5 Protein / metabolism
Smad8 Protein / metabolism
Transforming Growth Factor beta1 / metabolism*,  pharmacology
Grant Support
Reg. No./Substance:
0/Antigens, CD; 0/ENG protein, human; 0/Receptors, Cell Surface; 0/Receptors, Transforming Growth Factor beta; 0/SMAD1 protein, human; 0/SMAD2 protein, human; 0/SMAD3 protein, human; 0/SMAD5 protein, human; 0/SMAD8 protein, human; 0/Smad1 Protein; 0/Smad2 Protein; 0/Smad3 Protein; 0/Smad5 Protein; 0/Smad8 Protein; 0/Transforming Growth Factor beta1; EC type I receptor; EC Kinases; EC protein, human; EC Receptors, Type II; EC Morphogenetic Protein Receptors, Type I

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