Abstract
To define the role of transforming growth factor-beta 1 (TGF-beta 1) in modulating pericyte contractile phenotype, we have ablated the TGF-beta signaling pathway by infection with a retrovirus bearing a TGF-beta type II receptor with a truncated C-terminal intracellular kinase domain (DNT beta RII). While TGF-beta 1 blocks pericyte proliferation and induces the expression of vascular smooth muscle contractile proteins in wild-type pericytes, DNT beta RII-bearing pericytes are neither growth inhibited by TGF-beta 1 nor do they accumulate alpha-smooth muscle actin (alpha-SMA) mRNA or protein. TGF-beta 1 induces expression of the myogenic transcription factor myf-5 and the cyclin-dependent kinase inhibitor p27; we show that these signaling pathways are disrupted in the DNT beta RII-bearing pericytes. These observations demonstrate that the TGF-beta 1 signaling pathway controls pericyte growth state and contractile phenotype.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actins / metabolism
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Animals
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Blotting, Western
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Cattle
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Cell Differentiation
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Cell Division
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Cells, Cultured
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DNA Primers / pharmacology
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DNA-Binding Proteins*
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Fluorescent Antibody Technique, Indirect
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Gene Expression Regulation*
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Genes, Dominant
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Mice
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Microfilament Proteins / metabolism
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Microscopy, Fluorescence
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Muscle Proteins / metabolism
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Muscle, Smooth / metabolism
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Muscle, Smooth, Vascular / cytology
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Mutation
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Myogenic Regulatory Factor 5
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Pericytes / metabolism*
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Phenotype
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Protein Serine-Threonine Kinases
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Protein Structure, Tertiary
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RNA, Messenger / metabolism
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Receptor, Transforming Growth Factor-beta Type II
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Receptors, Transforming Growth Factor beta / metabolism
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Retina / cytology
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Retina / metabolism*
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Retroviridae / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction*
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Trans-Activators*
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Transforming Growth Factor beta / metabolism*
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Transforming Growth Factor beta1
Substances
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Actins
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DNA Primers
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DNA-Binding Proteins
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Microfilament Proteins
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Muscle Proteins
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Myf5 protein, mouse
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Myogenic Regulatory Factor 5
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RNA, Messenger
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Receptors, Transforming Growth Factor beta
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Tagln protein, mouse
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Tgfb1 protein, mouse
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Trans-Activators
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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Protein Serine-Threonine Kinases
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Receptor, Transforming Growth Factor-beta Type II