PMID- 17581219
OWN - NLM
STAT- MEDLINE
DCOM- 20070801
LR  - 20071115
IS  - 0305-1870 (Print)
IS  - 0305-1870 (Linking)
VI  - 34
IP  - 7
DP  - 2007 Jul
TI  - Hypoxia-induced astrocytes promote the migration of neural progenitor cells via 
      vascular endothelial factor, stem cell factor, stromal-derived factor-1alpha and 
      monocyte chemoattractant protein-1 upregulation in vitro.
PG  - 624-31
AB  - 1. The aim of the present study was to examine if and how rat hypoxia-induced 
      astrocytes affect the migration of neural progenitor cells (NPC) and to 
      investigate the expression patterns of some chemokines, such as vascular 
      endothelial growth factor (VEGF), stem cell factor (SCF), stromal-derived 
      factor-1alpha (SDF-1alpha), fractalkine and monocyte chemoattractant protein-1 
      (MCP-1) in hypoxia-induced astrocytes and their contribution to NPC migration in 
      vitro. 2. Costar Transwell inserts were used for the chemotaxis assay and 
      quantified changes in the chemokines mRNA for between 0 h and 24 h posthypoxia 
      were tested using real-time quantitative reverse transcriptase-polymerase chain 
      reaction (RT-PCR) analysis. The results showed that the chemotaxis of astrocyte 
      cells exposed to hypoxia for 18 h reached a peak value, whereas the chemotaxis of 
      astrocytes exposed to hypoxia for 24 h began to decrease compared with those 
      exposed to hypoxia for 18 h. Hypoxia upregulated chemokine VEGF, SCF, SDF-1alpha 
      and MCP-1 expression in a time-dependent manner but downregulated fractalkine 
      expression in astrocytes. In addition, the time points of the peak expressions 
      for VEGF, SCF, SDF-1alpha and MCP-1 were similar to the time point of maximum NPC 
      migration. 3. Specific inhibitors that block the binding of specific chemokines 
      to its receptors were used for analysing the contribution of the chemokine to NPC 
      migration. When VEGF, SCF, SDF-1alpha and MCP-1 were each inhibited 
      independently, NPC migration was reduced. When they were inhibited together, NPC 
      migration was obviously inhibited compared with both the control and single-block 
      cultures, which implies that the migratory effect of hypoxia-induced astrocytes 
      was synergetic by several chemokines. 4. In conclusion, we demonstrated the 
      time-dependent manner of NPC migration promotion by hypoxia-induced astrocytes. 
      We also provide evidence that soluble factors, such as VEGF, SCF, SDF-1alpha and 
      MCP-1, released from astrocytes, direct the migration of NPC under hypoxic 
      circumstances. Given that astrocytes were activated to all hypoxia-ischaemia 
      diseases, these results indicate an important role for astrocytes in directing 
      NPC replacement therapy in the central nervous system.
FAU - Xu, Qiang
AU  - Xu Q
AD  - Institute of Traditional Chinese Medicine, Suzuka University of Medical Science, 
      Suzuka, Mie, Japan.
FAU - Wang, Shaoxia
AU  - Wang S
FAU - Jiang, Xijuan
AU  - Jiang X
FAU - Zhao, Yali
AU  - Zhao Y
FAU - Gao, Ming
AU  - Gao M
FAU - Zhang, Yanjun
AU  - Zhang Y
FAU - Wang, Xiaoming
AU  - Wang X
FAU - Tano, Kaori
AU  - Tano K
FAU - Kanehara, Masayuki
AU  - Kanehara M
FAU - Zhang, Wenping
AU  - Zhang W
FAU - Ishida, Torao
AU  - Ishida T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Australia
TA  - Clin Exp Pharmacol Physiol
JT  - Clinical and experimental pharmacology & physiology
JID - 0425076
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CX3CL1)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Chemokines, CX3C)
RN  - 0 (Chemokines, CXC)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Cx3cl1 protein, rat)
RN  - 0 (Membrane Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Stem Cell Factor)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (vascular endothelial growth factor A, rat)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Astrocytes/*metabolism
MH  - Cell Differentiation
MH  - Cell Hypoxia
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology/metabolism
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Chemokine CX3CL1
MH  - Chemokine CXCL12
MH  - Chemokines, CX3C/metabolism
MH  - Chemokines, CXC/genetics/*metabolism
MH  - *Chemotaxis
MH  - Coculture Techniques
MH  - Culture Media, Conditioned/metabolism
MH  - Down-Regulation
MH  - Membrane Proteins/metabolism
MH  - Neurons/*metabolism
MH  - Paracrine Communication
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Stem Cell Factor/genetics/*metabolism
MH  - Stem Cells/*metabolism
MH  - Time Factors
MH  - Up-Regulation
MH  - Vascular Endothelial Growth Factor A/genetics/*metabolism
EDAT- 2007/06/22 09:00
MHDA- 2007/08/02 09:00
CRDT- 2007/06/22 09:00
PHST- 2007/06/22 09:00 [pubmed]
PHST- 2007/08/02 09:00 [medline]
PHST- 2007/06/22 09:00 [entrez]
AID - CEP4619 [pii]
AID - 10.1111/j.1440-1681.2007.04619.x [doi]
PST - ppublish
SO  - Clin Exp Pharmacol Physiol. 2007 Jul;34(7):624-31. doi: 
      10.1111/j.1440-1681.2007.04619.x.