Platelet-derived growth factor induces apoptosis in vascular smooth muscle cells: roles of the Bcl-2 family.
Apoptosis (programmed cell death) is observed in vascular smooth muscle cells (VSMC) in atherosclerotic lesions and stenotic lesions after injury, and modulates the cellularity of these lesions. It is recognized that cell growth and apoptosis are two linked processes. Platelet-derived growth factor (PDGF) induces VSMC proliferation and migration in vitro. We studied the effect of PDGF on apoptosis in VSMC. Cultured rat VSMC were treated with PDGF-AA or PDGF-BB. PDGF-BB induced cell death in cultured VSMC in a time- and dose-dependent manner, but PDGF-AA did not. Gel electrophoresis of genomic DNA and in situ DNA labeling confirmed that the cell death induced by PDGF-BB is apoptosis. PDGF-BB treatment reduced bcl-2 mRNA and bcl-xl mRNA expression, in contrast, induced bcl-xs mRNA expression, linked with the induction of apoptosis in cultured VSMC.
Okura
T
T
Second Department of Internal Medicine, Ehime University School of Medicine, Onsen-gun, Ehime 791-0295, Japan. okura@m.ehime-u.ac.jp
Igase
M
M
Kitami
Y
Y
Fukuoka
T
T
Maguchi
M
M
Kohara
K
K
Hiwada
K
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation; D015870:Gene Expression; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D010982:Platelet-Derived Growth Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D011994:Recombinant Proteins; C075278:platelet-derived growth factor A; D000077214:Becaplermin