Transforming growth factor-beta(1) induces apoptosis via connective tissue growth factor in human aortic smooth muscle cells.
We examined the possible involvement of connective tissue growth factor (CTGF) in the apoptosis induced by transforming growth factor-beta(1) (TGF-beta(1)) in human aortic vascular smooth muscle cells (HASC). In quiescent HASC, TGF-beta(1) induced the mRNA and protein of CTGF. A CTGF antisense oligonucleotide inhibited this induction. TGF-beta(1) significantly reduced cell viability and induced DNA fragmentation, and the CTGF antisense oligonucleotide reversed these effects. Moreover, TGF-beta(1) activated caspase 3 in HASC, and the CTGF antisense oligonucleotide reduced this activation. These findings show that CTGF plays a key role in the TGF-beta(1)-induced apoptosis in HASC.
Hishikawa
K
K
Department of Pharmacology, Teikyo University School of Medicine, Kaga 2-11-1, Itabashi-ku, Tokyo, Japan. hisikawa@med.teikyo-u.ac.jp
Nakaki
T
T
Fujii
T
T
D001011:Aorta / Q000166:cytology / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006133:Growth Substances / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
C526317:CCN2 protein, human; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases