Abstract
Smooth muscle cells (SMCs) are major components of blood vessels and other hollow visceral organs required for tissue engineering of these organs. This study aims to evaluate whether adult bone marrow-derived mesenchymal stem cells (BMMSCs), multipotent cells, can be converted into SMCs. We examined the ERK/MAPK pathway as it exerts anti-myogenic signals in SMCs. Undifferentiated BMMSCs express most SMC marker genes, albeit mainly at low levels, except smooth muscle myosin heavy chain (SMMHC), the most definitive marker of differentiated SMC. The treatment of BMMSC with MEK inhibitor up-regulated the expression of alpha-smooth muscle actin (ASMA), h-caldesmon, and SMMHC in BMMSC in low serum condition. MEK inhibitor-treated BMMSC also contracted a collagen gel in response to endothelin. Interestingly, inhibition of MEK induced myocardin expression in BMMSC. In conclusion, BMMSCs treated MEK inhibitor gain a SMC-like phenotype with ligand-induced cell contractility to endothelin in vitro. This approach has obvious implications for cell therapeutics and tissue engineering of hollow visceral organs such as blood vessels.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism
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Becaplermin
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Bone Marrow Cells / cytology*
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Bone Marrow Cells / drug effects
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Bone Marrow Cells / enzymology
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Calmodulin-Binding Proteins / genetics
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Calmodulin-Binding Proteins / metabolism
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Cell Differentiation* / drug effects
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Cell Lineage* / drug effects
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Cells, Cultured
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Collagen / metabolism
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Endothelins / pharmacology
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors*
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Gap Junctions / drug effects
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Gap Junctions / metabolism
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Gels
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Gene Expression Regulation / drug effects
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Humans
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MAP Kinase Signaling System* / drug effects
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Mesenchymal Stem Cells / cytology*
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Mesenchymal Stem Cells / drug effects
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Mesenchymal Stem Cells / enzymology
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Microfilament Proteins / genetics
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Microfilament Proteins / metabolism
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Muscle Development / drug effects
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Muscle Proteins / genetics
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Muscle Proteins / metabolism
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Myocytes, Smooth Muscle / cytology*
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Myocytes, Smooth Muscle / drug effects
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Myosin Heavy Chains / genetics
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Myosin Heavy Chains / metabolism
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Platelet-Derived Growth Factor / pharmacology
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Protein Kinase Inhibitors / pharmacology
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Proto-Oncogene Proteins c-sis
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism
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ets-Domain Protein Elk-1 / genetics
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ets-Domain Protein Elk-1 / metabolism
Substances
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Actins
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Calmodulin-Binding Proteins
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ELK1 protein, human
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Endothelins
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Gels
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Microfilament Proteins
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Muscle Proteins
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Nuclear Proteins
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Platelet-Derived Growth Factor
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins c-sis
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RNA, Messenger
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Trans-Activators
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Transcription Factors
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ets-Domain Protein Elk-1
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myocardin
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transgelin
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Becaplermin
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Collagen
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Extracellular Signal-Regulated MAP Kinases
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Myosin Heavy Chains