PMID- 19531492
OWN - NLM
STAT- MEDLINE
DCOM- 20091006
LR  - 20211203
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 284
IP  - 34
DP  - 2009 Aug 21
TI  - Kruppel-like factor 4 inhibits proliferation by platelet-derived growth factor 
      receptor beta-mediated, not by retinoic acid receptor alpha-mediated, 
      phosphatidylinositol 3-kinase and ERK signaling in vascular smooth muscle cells.
PG  - 22773-85
LID - 10.1074/jbc.M109.026989 [doi]
AB  - Proliferation inhibition of vascular smooth muscle cells (VSMCs) is governed by 
      the activity of a transcription factor network. Kruppel-like factor 4 (Klf4), 
      retinoic acid receptor (RAR alpha), and platelet-derived growth factor receptor 
      (PDGFR) are expressed in VSMCs and are components of such a network. However, the 
      relationship among them in the regulation of VSMC proliferation remains unknown. 
      Here, we investigated the mechanisms whereby Klf4 mediates the growth inhibitory 
      effects in VSMCs through RAR alpha and PDGFR beta. We demonstrated that Klf4 
      directly binds to the 5' regulatory region of RAR alpha, down-regulates RAR alpha 
      expression, and specifically inhibits RAR alpha-mediated phosphatidylinositol 
      3-kinase (PI3K) and ERK signaling in cultured VSMCs induced by the synthetic 
      retinoid Am80. Of particular interest, Klf4 inhibits RAR alpha and PDGFR beta 
      expression while blocking PI3K and ERK signaling induced by Am80 and PDGF-BB, 
      respectively. The anti-proliferative effects of Klf4 on neointimal formation 
      depend largely on PDGFR-mediated PI3K signaling without involvement of the RAR 
      alpha-activated signaling pathways. These findings provide a novel mechanism for 
      signal suppression and growth inhibitory effects of Klf4 in VSMCs. Moreover, the 
      results of this study suggest that Klf4 is one of the key mediators of retinoid 
      actions in VSMCs.
FAU - Zheng, Bin
AU  - Zheng B
AD  - Department of Biochemistry and Molecular Biology, Hebei Medical University, 
      Zhongshan East Road, Shijiazhuang 050017, China.
FAU - Han, Mei
AU  - Han M
FAU - Bernier, Michel
AU  - Bernier M
FAU - Zhang, Xin-hua
AU  - Zhang XH
FAU - Meng, Fang
AU  - Meng F
FAU - Miao, Sui-bing
AU  - Miao SB
FAU - He, Ming
AU  - He M
FAU - Zhao, Xin-ming
AU  - Zhao XM
FAU - Wen, Jin-kun
AU  - Wen JK
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090616
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (KLF4 protein, human)
RN  - 0 (Klf4 protein, rat)
RN  - 0 (Kruppel-Like Factor 4)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (RARA protein, human)
RN  - 0 (Rara protein, rat)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Chromatin Immunoprecipitation
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Kruppel-Like Factor 4
MH  - Kruppel-Like Transcription Factors/genetics/*physiology
MH  - Male
MH  - Muscle, Smooth, Vascular/*cytology
MH  - Mutagenesis, Site-Directed
MH  - Myocytes, Smooth Muscle/*metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphorylation
MH  - Polymerase Chain Reaction
MH  - Promoter Regions, Genetic
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Platelet-Derived Growth Factor beta/genetics/*metabolism
MH  - Receptors, Retinoic Acid/*metabolism
MH  - Retinoic Acid Receptor alpha
MH  - Signal Transduction/genetics/physiology
PMC - PMC2755685
EDAT- 2009/06/18 09:00
MHDA- 2009/10/07 06:00
PMCR- 2010/08/21
CRDT- 2009/06/18 09:00
PHST- 2009/06/18 09:00 [entrez]
PHST- 2009/06/18 09:00 [pubmed]
PHST- 2009/10/07 06:00 [medline]
PHST- 2010/08/21 00:00 [pmc-release]
AID - S0021-9258(17)30782-2 [pii]
AID - M109.026989 [pii]
AID - 10.1074/jbc.M109.026989 [doi]
PST - ppublish
SO  - J Biol Chem. 2009 Aug 21;284(34):22773-85. doi: 10.1074/jbc.M109.026989. Epub 
      2009 Jun 16.