PMID- 20677223
OWN - NLM
STAT- MEDLINE
DCOM- 20110106
LR  - 20211203
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 226
IP  - 2
DP  - 2011 Feb
TI  - Role of hypoxia-induced fibronectin-integrin beta1 expression in embryonic stem cell 
      proliferation and migration: Involvement of PI3K/Akt and FAK.
PG  - 484-93
LID - 10.1002/jcp.22358 [doi]
AB  - Cell migration is largely dependent on integrin (IN) binding to the extracellular 
      matrix, and several signaling pathways involved in these processes have been 
      shown to be modified by hypoxia. Therefore, the aim of this study was to 
      determine the influence of hypoxia on fibronectin (FN) and IN beta1 expression in 
      mouse embryonic stem cells (mESCs) and their signaling pathways to modulate 
      proliferation. FN and IN beta1 expression were significantly increased in hypoxic 
      mESCs by 24 h. Hypoxia also increased cell attachment, which was accompanied by 
      concomitant increases in the binding level of FN and IN beta1. Hypoxia-induced FN 
      expression was mediated by increased phosphatidylinositol 3 kinase (PI3K)/Akt and 
      mammalian target of rapamycin (mTOR) phosphorylation, and hypoxia-inducible 
      factor-1alpha (HIF-1alpha) expression. Moreover, under hypoxic conditions, focal adhesion 
      kinase (FAK) and Src phosphorylation were increased in a time-dependent fashion; 
      these increases were blocked by IN beta1 antibody. In addition, the hypoxia induced 
      increase of F-actin distribution and cell migration (activation of matrix 
      metalloproteinase-2 and -9) was inhibited by IN beta1 antibody. Indeed, hypoxia 
      increased the level of cell-cycle regulatory protein and DNA synthesis. In 
      conclusion, hypoxia increases the proliferation and migration of mESCs via FN-IN 
      beta1 production through the PI3K/Akt, mTOR, and HIF-1alpha pathways, followed by FAK 
      activation.
CI  - (c) 2010 Wiley-Liss, Inc.
FAU - Lee, Sang Hun
AU  - Lee SH
AD  - Department of Veterinary Physiology, Biotherapy Human Resources Center (BK 21), 
      College of Veterinary Medicine, Chonnam National University, Gwangju, Korea.
FAU - Lee, Yu Jin
AU  - Lee YJ
FAU - Han, Ho Jae
AU  - Han HJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Fibronectins)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Integrin beta1)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - *Cell Hypoxia
MH  - Cell Movement/*physiology
MH  - Cell Proliferation
MH  - Embryonic Stem Cells/cytology/*physiology
MH  - Fibronectins/genetics/*metabolism
MH  - Focal Adhesion Protein-Tyrosine Kinases/genetics/*metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism
MH  - Integrin beta1/genetics/*metabolism
MH  - Matrix Metalloproteinase 2/genetics/metabolism
MH  - Matrix Metalloproteinase 9/genetics/metabolism
MH  - Mice
MH  - Phosphatidylinositol 3-Kinases/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/*metabolism
MH  - Signal Transduction/physiology
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
EDAT- 2010/08/03 06:00
MHDA- 2011/01/07 06:00
CRDT- 2010/08/03 06:00
PHST- 2010/08/03 06:00 [entrez]
PHST- 2010/08/03 06:00 [pubmed]
PHST- 2011/01/07 06:00 [medline]
AID - 10.1002/jcp.22358 [doi]
PST - ppublish
SO  - J Cell Physiol. 2011 Feb;226(2):484-93. doi: 10.1002/jcp.22358.