PMID- 8940178
OWN - NLM
STAT- MEDLINE
DCOM- 19970109
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 271
IP  - 49
DP  - 1996 Dec 6
TI  - Transcriptional regulation by transforming growth factor beta of the expression 
      of retinoic acid and retinoid X receptor genes in osteoblastic cells is mediated 
      through AP-1.
PG  - 31602-6
AB  - We now report that transforming growth factor beta1 (TGF-beta1), a potent 
      regulatory cytokine of bone remodeling, is a powerful stimulator for gene 
      expression of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in 
      osteoblastic MC3T3-E1 cells. TGF-beta1 transcriptionally stimulated the 
      expression of RARalpha, RARgamma, and RXRalpha genes, but did not do so for 
      RARbeta, RXRbeta, and RXRgamma genes. We also observed that AP-1, a 
      transcriptional factor, plays an important role in the signal pathway for 
      expression of RARalpha, RARgamma, and RXRalpha genes stimulated by TGF-beta1 
      because stimulation of the expression of these genes in the cytokine-treated 
      cells was markedly inhibited by a mixture of antisense c-fos and c-jun. A gel 
      mobility shift assay demonstrated that TGF-beta1 is able to increase, in a 
      dose-dependent manner, the binding of nuclear proteins to direct repeat 5, a 
      consensus sequence with high affinity for RAR-RXR heterodimers. The mobility 
      shift assay, using specific antibody for each receptor, showed that direct repeat 
      5-binding proteins may be RAR and RXR isoforms. The stimulated binding to direct 
      repeat 5 was inhibited strongly by H-7, an inhibitor of serine/threonine kinase, 
      and by curcumin, an inhibitor of AP-1. The present study suggests a novel pathway 
      for TGF-beta1 action in osteoblastic cells via stimulation of RAR-RXR 
      transcriptional activity in a ligand-dependent fashion.
FAU - Chen, Y
AU  - Chen Y
AD  - Department of Oral Microbiology, Meikai University School of Dentistry, 
      Keyakidai, Sakado City, Saitama 350-02, Japan.
FAU - Takeshita, A
AU  - Takeshita A
FAU - Ozaki, K
AU  - Ozaki K
FAU - Kitano, S
AU  - Kitano S
FAU - Hanazawa, S
AU  - Hanazawa S
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Transcription Factors)
RN  - 0 (Transforming Growth Factor beta)
RN  - 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/pharmacology
MH  - Animals
MH  - Binding, Competitive
MH  - Blotting, Northern
MH  - Cell Line
MH  - Curcumin/pharmacology
MH  - DNA-Binding Proteins/*genetics
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Mice
MH  - Nuclear Proteins/*genetics
MH  - Osteoblasts/*metabolism
MH  - Receptors, Retinoic Acid/*genetics
MH  - Retinoid X Receptors
MH  - Transcription Factor AP-1/antagonists & inhibitors/*metabolism
MH  - Transcription Factors/*genetics
MH  - *Transcription, Genetic
MH  - Transforming Growth Factor beta/*metabolism
EDAT- 1996/12/06 00:00
MHDA- 1996/12/06 00:01
CRDT- 1996/12/06 00:00
PHST- 1996/12/06 00:00 [pubmed]
PHST- 1996/12/06 00:01 [medline]
PHST- 1996/12/06 00:00 [entrez]
AID - S0021-9258(19)79031-0 [pii]
AID - 10.1074/jbc.271.49.31602 [doi]
PST - ppublish
SO  - J Biol Chem. 1996 Dec 6;271(49):31602-6. doi: 10.1074/jbc.271.49.31602.