B-Myb represses elastin gene expression in aortic smooth muscle cells.
B-Myb represses collagen gene transcription in vascular smooth muscle cells (SMCs) in vitro and in vivo. Here we sought to determine whether elastin is similarly repressed by B-Myb. Levels of tropoelastin mRNA and protein were lower in aortas and isolated SMCs of adult transgenic mice expressing the human B-myb gene, driven by the basal cytomegalovirus promoter, compared with age-matched wild type (WT) animals. However, the vessel wall architecture and levels of insoluble elastin revealed no differences. Since elastin deposition occurs early in development, microarray analysis was performed using nontransgenic mice. Aortic levels of tropoelastin mRNA were low during embryonal growth and increased substantially in neonates, whereas B-myb levels varied inversely. Tropoelastin mRNA expression in aortas of 6-day-old neonatal transgenic and WT animals was comparable. Recently, we demonstrated that cyclin A-Cdk2 prevents B-Myb-mediated repression of collagen promoter activity. Cyclin A2 levels were higher in neonatal versus adult WT or transgenic mouse aortas. Ectopic cyclin A expression reversed the ability of B-Myb to repress elastin gene promoter activity in adult SMCs. These results demonstrate for the first time that B-Myb represses SMC elastin gene expression and that cyclin A plays a role in the developmental regulation of elastin gene expression in the aorta. Furthermore, the findings provide additional insight into the mechanism of B-myb-mediated resistance to femoral artery injury.
Hofmann
Claudia S
CS
Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Wang
Xiaobo
X
Sullivan
Christopher P
CP
Toselli
Paul
P
Stone
Phillip J
PJ
McLean
Sean E
SE
Mecham
Robert P
RP
Schreiber
Barbara M
BM
Sonenshein
Gail E
GE
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology*; D015152:Blotting, Northern; D002417:Cattle; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D019925:Cyclin A / Q000378:metabolism; D056751:Cyclin A2; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004549:Elastin / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005269:Femur / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D014333:Tropoelastin / Q000378:metabolism
C503721:CCNA2 protein, human; D018797:Cell Cycle Proteins; D019925:Cyclin A; D056751:Cyclin A2; D004268:DNA-Binding Proteins; C064352:MYBL2 protein, human; C499306:Mybl2 protein, mouse; D012333:RNA, Messenger; D015534:Trans-Activators; D014333:Tropoelastin; D012313:RNA; D003094:Collagen; D004549:Elastin