Expression of a novel RNA-splicing factor, RA301/Tra2beta, in vascular lesions and its role in smooth muscle cell proliferation.
RA301/Tra2beta, a sequence-specific RNA-binding protein, was first cloned as a stress molecule in re-oxygenated astrocytes. In human vascular tissues, we have found enhanced RA301/Tra2beta expression in coronary artery with intimal thickening, and atherosclerotic aorta. Balloon injury to the rat carotid artery induced RA301/Tra2beta transcripts followed by expression of the antigen, which was detected in medial and neointimal vascular smooth muscle cells (VSMCs). In cultured VSMCs, hypoxia/re-oxygenation caused induction of RA301/Tra2beta and was accompanied by cell proliferation, both of which were blocked by the addition of either diphenyl iodonium, a NADPH oxidase inhibitor, PD98059, a mitogen-activated protein kinase kinase inhibitor, or antisense oligonucleotide for RA301/Tra2beta. Consistent with a link between RA301/Tra2beta and cell proliferation, platelet-derived growth factor also induced expression of RA301/Tra2beta in cultured VSMCS: These data suggest a possible role for RA301/Tra2beta in the regulation of VSMC proliferation, especially in the setting of hypoxia/re-oxygenation-induced cell stress.
Tsukamoto
Y
Y
Department of Pathology and Neurosurgery, National Cardiovascular Center, Suita City, Japan. ytukamot@hsp.ncvc.go.jp
Matsuo
N
N
Ozawa
K
K
Hori
O
O
Higashi
T
T
Nishizaki
J
J
Tohnai
N
N
Nagata
I
I
Kawano
K
K
Yutani
C
C
Hirota
S
S
Kitamura
Y
Y
Stern
D M
DM
Ogawa
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D016373:DNA, Antisense / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D009861:Onium Compounds / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068103:Serine-Arginine Splicing Factors; D013481:Superoxides / Q000378:metabolism
D001713:Biphenyl Compounds; D016373:DNA, Antisense; D005419:Flavonoids; D009419:Nerve Tissue Proteins; D009861:Onium Compounds; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C097083:TRA2B protein, human; C490770:Tra2b protein, rat; C031291:diphenyliodonium; D013481:Superoxides; D000068103:Serine-Arginine Splicing Factors; D010100:Oxygen; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one