PMID- 24880525
OWN - NLM
STAT- MEDLINE
DCOM- 20150109
LR  - 20140616
IS  - 1618-1298 (Electronic)
IS  - 0171-9335 (Linking)
VI  - 93
IP  - 4
DP  - 2014 Apr
TI  - Epigallocatechin-3-gallate inhibits proliferation of human aortic smooth muscle 
      cells via up-regulating expression of mitofusin 2.
PG  - 137-44
LID - S0171-9335(14)00050-8 [pii]
LID - 10.1016/j.ejcb.2014.04.001 [doi]
AB  - Previous studies have shown that epigallocatechin-3-gallate (EGCG) inhibits the 
      proliferation of vascular smooth muscle cells (VSMCs) via the 
      extracellular-signal-regulated kinase (ERK1/2) and mitogen activated protein 
      kinases (MAPKs) pathway. Mitofusin 2 (Mfn-2) also suppresses VSMC proliferation 
      through Ras-Raf-ERK/MAPK, suggesting a possible link between EGCG, Mfn-2 and 
      ERK/MAPK. However, the effect of EGCG on Mfn-2 remains unknown. In this study, we 
      investigated the role of Mfn-2 in the regulation of VSMC proliferation by EGCG, 
      and assessed the underlying mechanisms. The effects of EGCG on the proliferation 
      of cultured human aortic smooth muscle cells (HASMCs) were observed by 
      5-ethynl-2-deoxyuridine (EdU) incorporation assay. Mfn-2 gene and protein levels, 
      and Ras, p-c-Raf and p-ERK1/2 protein levels were determined by quantitative 
      real-time polymerase chain reaction and western blotting, respectively. Mfn-2 
      gene silencing was achieved by RNA interference. EGCG 50 mumol/L profoundly 
      inhibited the proliferation of HASMCs in culture, up-regulated Mfn-2, and 
      down-regulated the expression of p-c-Raf and p-ERK1/2. Furthermore, RNA 
      interference-mediated gene knockdown of Mfn-2 antagonized EGCG-induced 
      anti-proliferation and down-regulation of Ras, p-c-Raf and p-ERK1/2. These 
      results suggest that EGCG inhibits the proliferation of HASMCs in vitro largely 
      via Mfn-2-mediated suppression of the Ras-Raf-ERK/MAPK signaling pathway.
CI  - Copyright (c) 2014 Elsevier GmbH. All rights reserved.
FAU - Shu, Zhouwu
AU  - Shu Z
AD  - Department of Cardiology, The First Affiliated Hospital of Shantou University 
      Medical College, Shantou, Guangdong 515041, China; Molecular Biology Laboratory, 
      The First Affiliated Hospital of Shantou University Medical College, Shantou, 
      Guangdong 515041, China.
FAU - Yu, Min
AU  - Yu M
AD  - Department of Cardiology, The First Affiliated Hospital of Shantou University 
      Medical College, Shantou, Guangdong 515041, China; Molecular Biology Laboratory, 
      The First Affiliated Hospital of Shantou University Medical College, Shantou, 
      Guangdong 515041, China.
FAU - Zeng, Guoning
AU  - Zeng G
AD  - Molecular Biology Laboratory, The First Affiliated Hospital of Shantou University 
      Medical College, Shantou, Guangdong 515041, China.
FAU - Zhang, Xin
AU  - Zhang X
AD  - Molecular Biology Laboratory, The First Affiliated Hospital of Shantou University 
      Medical College, Shantou, Guangdong 515041, China.
FAU - Wu, Libiao
AU  - Wu L
AD  - Molecular Biology Laboratory, The First Affiliated Hospital of Shantou University 
      Medical College, Shantou, Guangdong 515041, China.
FAU - Tan, Xuerui
AU  - Tan X
AD  - Department of Cardiology, The First Affiliated Hospital of Shantou University 
      Medical College, Shantou, Guangdong 515041, China. Electronic address: 
      shuzhw@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140509
PL  - Germany
TA  - Eur J Cell Biol
JT  - European journal of cell biology
JID - 7906240
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 8R1V1STN48 (Catechin)
RN  - BQM438CTEL (epigallocatechin gallate)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
RN  - EC 2.7.11.24 (MAPK1 protein, human)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (MFN2 protein, human)
SB  - IM
MH  - Aorta/cytology/drug effects
MH  - Catechin/*analogs & derivatives/pharmacology
MH  - Cell Line
MH  - Cell Proliferation/*drug effects
MH  - GTP Phosphohydrolases/genetics/*metabolism
MH  - Humans
MH  - Mitochondrial Proteins/genetics/*metabolism
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Myocytes, Smooth Muscle/cytology/*drug effects
MH  - Proto-Oncogene Proteins c-raf/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Up-Regulation
OTO - NOTNLM
OT  - Epigallocatechin-3-gallate
OT  - Human aortic smooth muscle cell
OT  - Mitofusin 2
OT  - Proliferation
OT  - Ras-Raf-ERK/MAPK
OT  - siRNA
EDAT- 2014/06/02 06:00
MHDA- 2015/01/13 06:00
CRDT- 2014/06/02 06:00
PHST- 2013/11/27 00:00 [received]
PHST- 2014/04/23 00:00 [revised]
PHST- 2014/04/24 00:00 [accepted]
PHST- 2014/06/02 06:00 [entrez]
PHST- 2014/06/02 06:00 [pubmed]
PHST- 2015/01/13 06:00 [medline]
AID - S0171-9335(14)00050-8 [pii]
AID - 10.1016/j.ejcb.2014.04.001 [doi]
PST - ppublish
SO  - Eur J Cell Biol. 2014 Apr;93(4):137-44. doi: 10.1016/j.ejcb.2014.04.001. Epub 
      2014 May 9.