NDLI: Thromboxane a(2) induces differentiation of human mesenchymal stem cells to smooth muscle-like cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kim, Mi Ra Jeon, Eun Su Kim, Young Mi Lee, Jung Sub Kim, Jae Ho
Description	Author Affiliation: Kim MR ( Medical Research Center for Ischemic Tissue Regeneration, the Medical Research Institute, Department of Physiology, Busan, Republic of Korea.)
Abstract	Thromboxane A(2) (TxA(2)) is involved in smooth muscle contraction and atherosclerotic vascular diseases. Accumulating evidence suggests a pivotal role for mesenchymal stem cells (MSCs) in vascular remodeling. In the present study, we demonstrate for the first time that the TxA(2) mimetic U46619 induces differentiation of human adipose tissue-derived MSCs (hADSCs) to smooth muscle-like cells, as demonstrated by increased expression of smooth muscle-specific contractile proteins such as alpha-smooth muscle actin (alpha-SMA), calponin, smoothelin, and smooth muscle-myosin heavy chain. Using an in vitro collagen gel lattice contraction assay, we showed that U46619-induced expression of the contractile proteins was associated with increased contractility of the cells. U46619 increased the intracellular Ca(2+) concentration in hADSCs and pretreatment of the cells with the thromboxane receptor antagonist SQ29548 or the calmodulin (CaM) inhibitor W13 abrogated the U46619-induced alpha-SMA expression and contractility, suggesting a pivotal role of Ca(2+)/CaM in the U46619-stimulated smooth muscle differentiation of hADSCs. In addition, U46619 elicited activation of RhoA in hADSCs, and pretreatment of the cells with the Rho kinase-specific inhibitor Y27632 or overexpression of the dominant-negative mutants of RhoA and Rho kinase blocked U46619-stimulated alpha-SMA expression and contractility. Furthermore, U46619 induced phosphorylation of myosin light chain (MLC) through CaM/MLC kinase- and Rho kinase-dependent pathways, and the MLC kinase inhibitor ML-7 abrogated U46619-induced alpha-SMA expression and contractility. These results suggest that U46619 induces differentiation of hADSCs to contractile smooth muscle-like cells through CaM/MLCK- and RhoA-Rho kinase-dependent actin polymerization.
File Format	HTM / HTML
ISSN	10665099
Issue Number	1
Volume Number	27
e-ISSN	15494918
Journal	STEM CELLS
Language	English
Publisher	Wiley
Publisher Date	2009-01-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Discipline Cell Biology Discipline Embryology Cell Differentiation Drug Effects Mesenchymal Stromal Cells Cytology Myocytes, Smooth Muscle Thromboxane A2 Pharmacology 15-hydroxy-11 Alpha,9 Alpha-(epoxymethano)prosta-5,13-dienoic Acid Actins Metabolism Adipose Tissue Calcium Humans Enzymology Muscle Contraction Myosin Light Chains Nuclear Proteins Receptors, Thromboxane Serum Response Factor Stress Fibers Trans-activators Rho-associated Kinases Rhoa Gtp-binding Protein Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject Domain (in MeSH)	Tissues Cells Eukaryota Inorganic Chemicals Macromolecular Substances Enzymes and Coenzymes Lipids Amino Acids, Peptides, and Proteins Cell Physiological Phenomena Musculoskeletal and Neural Physiological Phenomena
Subject	Molecular Medicine Developmental Biology Cell Biology Medicine

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