PMID- 17467690
OWN - NLM
STAT- MEDLINE
DCOM- 20070817
LR  - 20121115
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 313
IP  - 11
DP  - 2007 Jul 1
TI  - Epidermal growth factor and transforming growth factor-beta1 enhance HK-2 cell 
      migration through a synergistic increase of matrix metalloproteinase and 
      sustained activation of ERK signaling pathway.
PG  - 2367-77
AB  - Epidermal growth factor (EGF) and transforming growth factor-beta1 (TGF-beta1), 
      upregulated in renal diseases, have a combinational effect on 
      epithelial-mesenchymal transformation (EMT) of renal proximal tubular cells. The 
      aim of this study was to examine the mechanism regarding the combinational effect 
      of EGF and TGF-beta1 on cell migration following EMT. The results demonstrated 
      that EGF (10 ng/ml) and TGF-beta1 (3 ng/ml) synergistically increased cell 
      migration, accompanied by an increase in matrix metalloproteinase-9 (MMP-9) gene 
      expression, production and activity. Inhibition of MMP-9 production and activity 
      by an MMP-2/MMP-9-specific inhibitor blocked the synergistic effect of EGF and 
      TGF-beta1 on cell migration. The kinetic profile of extracellular 
      signal-regulated kinase (ERK) signals demonstrated that ERK1/2 activation was 
      rapidly and strongly induced by EGF but delayed and less marked by TGF-beta1 
      stimulation. In contrast, co-administration of EGF and TGF-beta1 caused an early 
      pronounced and persistent ERK1/2 activation. Inhibition of the ERK1/2 activity by 
      PD98059 abrogated the synergistic effect of EGF and TGF-beta1 on cell migration, 
      MMP-9 production and activity, indicating that EGF and TGF-beta1 converged at the 
      ERK signaling pathway to mediate cell migration. This study demonstrates that EGF 
      and TGF-beta1 synergistically stimulate proximal tubular cell migration through 
      the increased MMP-9 function and enhanced ERK1/2 activation.
FAU - Tian, Ya-Chung
AU  - Tian YC
AD  - Kidney Institute, Department of Nephrology, Chang Gung Memorial Hospital, Taipei, 
      Taiwan. dryctian@adm.cgmh.org.tw
FAU - Chen, Yung-Chang
AU  - Chen YC
FAU - Chang, Chiz-Tzung
AU  - Chang CT
FAU - Hung, Cheng-Chieh
AU  - Hung CC
FAU - Wu, Mai-Szu
AU  - Wu MS
FAU - Phillips, Aled
AU  - Phillips A
FAU - Yang, Chih-Wei
AU  - Yang CW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070330
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Cell Line
MH  - *Cell Movement
MH  - Enzyme Inhibitors/pharmacology
MH  - Epidermal Growth Factor/*pharmacology
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Kidney Tubules/cytology/*drug effects/enzymology
MH  - Matrix Metalloproteinase 2/genetics/*metabolism
MH  - Matrix Metalloproteinase 9/genetics/*metabolism
MH  - Matrix Metalloproteinase Inhibitors
MH  - Signal Transduction
MH  - Transforming Growth Factor beta1/*pharmacology
EDAT- 2007/05/01 09:00
MHDA- 2007/08/19 09:00
CRDT- 2007/05/01 09:00
PHST- 2006/10/17 00:00 [received]
PHST- 2007/02/18 00:00 [revised]
PHST- 2007/03/22 00:00 [accepted]
PHST- 2007/05/01 09:00 [pubmed]
PHST- 2007/08/19 09:00 [medline]
PHST- 2007/05/01 09:00 [entrez]
AID - S0014-4827(07)00142-5 [pii]
AID - 10.1016/j.yexcr.2007.03.022 [doi]
PST - ppublish
SO  - Exp Cell Res. 2007 Jul 1;313(11):2367-77. doi: 10.1016/j.yexcr.2007.03.022. Epub 
      2007 Mar 30.