TGF-beta 1 signaling controls retinal pericyte contractile protein expression.
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.
Sieczkiewicz
Gregory J
GJ
Department of Physiology and Graduate Program in Cellular and Molecular Physiology, Tufts University School of Medicine, Boston, MA 02111, USA.
Herman
Ira M
IM
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D017931:DNA Primers / Q000494:pharmacology; D004268:DNA-Binding Proteins; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009124:Muscle Proteins / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009154:Mutation; D051787:Myogenic Regulatory Factor 5; D020286:Pericytes / Q000378:metabolism*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015534:Trans-Activators; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D000199:Actins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C058992:Tagln protein, mouse; C508961:Tgfb1 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II