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Integrin α5β1-Ang1/Tie2 receptor cross-talk regulates brain endothelial cell responses following cerebral ischemia
- Source :
- Experimental and Molecular Medicine, Vol 50, Iss 9, Pp 1-12 (2018)
- Publication Year :
- 2018
-
Abstract
- We have previously demonstrated that in response to cerebral ischemia (CI), the growth factor angiopoietin-1 (Ang1) and α5β1 integrin are both induced in cerebral vessels, which likely provide positive signals driving the endogenous angiogenic response and vascular protection after CI. However, the precise relationship between endothelial Ang1 and α5β1 integrin after CI remains poorly understood. Here, we investigated the effects of the interaction between the Ang1/Tie2 system and α5β1 integrin on brain endothelial cells (BECs) under cerebral ischemic conditions in vivo and in vitro. Immunofluorescence analysis demonstrated that integrin α5β1 co-localized with Tie2/phosphorylated Tie2 on cerebral vessels in the penumbra. The in vitro study showed that oxygen–glucose deprivation/restoration (OGD/R) induced the expression of the Ang1 receptor Tie2 on BECs in a manner similar to that for integrin α5 and Ang1 in response to OGD/R, accompanied by increased activation of Tie2 and its downstream effectors focal adhesion kinase (FAK) and Akt. Knockdown of α5 integrin markedly suppressed OGD/R-induced Tie2 receptor activation in BECs, while in contrast, priming BECs with Ang1 promoted the expression of α5 integrin as well as the Tie2 downstream transcription factor Ets-1 in OGD-treated BECs. In line with this, Ets-1 knockdown significantly attenuated Ang1-mediated upregulation of α5 integrin. Functionally, Ang1 induced cell migration and tube formation of BECs after OGD, but this effect was inhibited by diminishment of the levels of α5 integrin in BECs. Taken together, our data indicate that the Ang1/Tie2 system cross-talks with integrin α5β1 in BECs after CI, which may contribute to the endogenous angiogenic vascular protective response following CI.
- Subjects :
- 0301 basic medicine
Male
Time Factors
medicine.medical_treatment
Clinical Biochemistry
Integrin
lcsh:Medicine
Neovascularization, Physiologic
Biochemistry
Models, Biological
Brain Ischemia
Cell Line
lcsh:Biochemistry
Focal adhesion
Proto-Oncogene Protein c-ets-1
03 medical and health sciences
0302 clinical medicine
Cell Movement
medicine
Angiopoietin-1
Animals
lcsh:QD415-436
Molecular Biology
Protein kinase B
Tube formation
biology
Chemistry
Growth factor
lcsh:R
Brain
Endothelial Cells
Cell migration
Receptor, TIE-2
Cell biology
Endothelial stem cell
Mice, Inbred C57BL
Oxygen
030104 developmental biology
Glucose
Focal Adhesion Kinase 1
cardiovascular system
biology.protein
Molecular Medicine
Signal transduction
Proto-Oncogene Proteins c-akt
030217 neurology & neurosurgery
Integrin alpha5beta1
Signal Transduction
Subjects
Details
- ISSN :
- 20926413
- Volume :
- 50
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Experimentalmolecular medicine
- Accession number :
- edsair.doi.dedup.....064b7adda2fb31ca47c5f51002d1df80