PMID- 11827696
OWN - NLM
STAT- MEDLINE
DCOM- 20020311
LR  - 20190513
IS  - 0008-6363 (Print)
IS  - 0008-6363 (Linking)
VI  - 53
IP  - 2
DP  - 2002 Feb 1
TI  - Fibronectin signaling stimulates BNP gene transcription by inhibiting 
      neuron-restrictive silencer element-dependent repression.
PG  - 451-9
AB  - OBJECTIVE: Brain natriuretic peptide (BNP) is a cardiac hormone mainly 
      synthesized in ventricles and its expression is markedly increased in ventricular 
      hypertrophy that involves the accumulation of extracellular matrix proteins, such 
      as fibronectin (Fn). We recently reported that Fn signaling stimulated BNP 
      secretion accompanied by hypertrophic responses in vitro. METHODS: To elucidate 
      the regulatory mechanism for BNP gene transcription, we examined cis-acting 
      elements downstream of Fn signaling in rat ventricular myocytes transfected with 
      either the -1812 human BNP-luciferase reporter gene (-1812hBNP/Luc) or one of 
      several truncated forms. RESULTS: A strong cis-repressor element was identified 
      between -552 and -522 in myocytes plated on uncoated dishes. This region contains 
      a neuron-restrictive silencer element (NRSE)-like element (NRSE(BNP)) that is 90% 
      homologous with the NRSE consensus sequence. Neuron-restrictive silencer factor 
      (NRSF) is known to bind to NRSE and to silence transcription of genes containing 
      NRSE. Deletion of NRSE(BNP) and dominant negative NRSF markedly increased the 
      reporter activity in transfected cells, suggesting that the NRSE/NRSF system 
      silences basal BNP gene transcription. When myocytes were cultured on Fn-coated 
      dishes, the reporter activity of -1812hBNP/Luc was increased by approximately 
      600% compared with that on uncoated dishes. Interestingly, truncation from -552 
      to -522 reduced the Fn-inducible reporter activity. Moreover, deletion of 
      NRSE(BNP) and dominant negative NRSF also inhibited the Fn-inducible reporter 
      activity. Electrophoretic mobility shift assays showed that Fn signaling 
      inhibited the binding activity of NRSF to NRSE(BNP). CONCLUSION: These results 
      suggest that Fn-induced BNP up-regulation in rat ventricular myocytes is due to 
      inhibition of NRSE(BNP)-dependent repression of BNP gene transcription.
FAU - Ogawa, Emiko
AU  - Ogawa E
AD  - Department of Medicine and Clinical Science, Kyoto University Graduate School of 
      Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
FAU - Saito, Yoshihiko
AU  - Saito Y
FAU - Kuwahara, Koichiro
AU  - Kuwahara K
FAU - Harada, Masaki
AU  - Harada M
FAU - Miyamoto, Yoshihiro
AU  - Miyamoto Y
FAU - Hamanaka, Ichiro
AU  - Hamanaka I
FAU - Kajiyama, Noboru
AU  - Kajiyama N
FAU - Takahashi, Nobuki
AU  - Takahashi N
FAU - Izumi, Takehiko
AU  - Izumi T
FAU - Kawakami, Rika
AU  - Kawakami R
FAU - Kishimoto, Ichiro
AU  - Kishimoto I
FAU - Naruse, Yoshihisa
AU  - Naruse Y
FAU - Mori, Nozomu
AU  - Mori N
FAU - Nakao, Kazuwa
AU  - Nakao K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Fibronectins)
RN  - 0 (RE1-silencing transcription factor)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Extracellular Matrix/metabolism
MH  - Fibronectins/*metabolism
MH  - Gene Expression Regulation/physiology
MH  - Hypertrophy, Left Ventricular/*metabolism
MH  - Myocardium/*metabolism
MH  - Natriuretic Peptide, Brain/genetics/*metabolism
MH  - Protein Binding
MH  - Rats
MH  - Repressor Proteins/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/*physiology
MH  - Transcription Factors/*metabolism
MH  - Transcription, Genetic
EDAT- 2002/02/06 10:00
MHDA- 2002/03/12 10:01
CRDT- 2002/02/06 10:00
PHST- 2002/02/06 10:00 [pubmed]
PHST- 2002/03/12 10:01 [medline]
PHST- 2002/02/06 10:00 [entrez]
AID - S0008636301004928 [pii]
AID - 10.1016/s0008-6363(01)00492-8 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2002 Feb 1;53(2):451-9. doi: 10.1016/s0008-6363(01)00492-8.