Type 2 deiodinase expression is stimulated by growth factors in human vascular smooth muscle cells.
Type 2 deiodinase (D2) catalyzes the conversion of the prohormone T4 to the biologically active T3. D2 is expressed in human aortic smooth muscle cells (hASMCs). In this study, we demonstrated that the D2 mRNA and activity in hASMCs were up-regulated by platelet-derived growth factor-BB (PDGF-BB) and basic fibroblast growth factor (bFGF). The induction of D2 mRNA by PDGF-BB and bFGF was dependent on de novo RNA and protein synthesis. PD98059, a specific inhibitor of the upstream kinase that activates extracellular signal-regulated kinase (ERK), significantly suppressed the induction by both PDGF-BB and bFGF. SB203580, a specific inhibitor of p38 mitogen-activated protein (MAP) kinase, and SP600125, a specific inhibitor of c-Jun N-terminal kinase (JNK), also reduced the induction by both PDGF-BB and bFGF. These results suggest that both PDGF-BB and bFGF induce D2 expression at least partly via ERK pathway. The p38 MAP kinase and JNK pathways may also be involved in the induction.
Maeda
Akimasa
A
Department of Medicine II, Kansai Medical University, 10-15 Fumizono Cho, Moriguchi-City, Osaka 570, Japan.
Toyoda
Nagaoki
N
Yasuzawa-Amano
Saori
S
Iwasaka
Toshiji
T
Nishikawa
Mitsushige
M
D000873:Anthracenes / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007453:Iodide Peroxidase / Q000096:biosynthesis* / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D000097564:Iodothyronine Deiodinase Type II
D000873:Anthracenes; D003513:Cycloheximide; D003609:Dactinomycin; D016222:Fibroblast Growth Factor 2; D005419:Flavonoids; D007093:Imidazoles; D007453:Iodide Peroxidase; D020574:Proto-Oncogene Proteins c-sis; D011725:Pyridines; D012333:RNA, Messenger; D000097564:Iodothyronine Deiodinase Type II; C432165:pyrazolanthrone; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one