Angiopoietin 2 Mediates the Differentiation and Migration of Neural Progenitor Cells in the Subventricular Zone after Stroke*
| Autor: | Sara C. Gregg, Michael Chopp, Ann Hozeska-Solgot, Zheng Gang Zhang, Rui Lan Zhang, Xian Shuang Liu, Mei Lu, Ben Buller |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
Chromatin Immunoprecipitation Cellular differentiation Subventricular zone Gene Expression Biology In Vitro Techniques Biochemistry Angiopoietin-2 Mice Cell Movement Neurosphere Cell Line Tumor medicine Animals Humans Progenitor cell RNA Small Interfering Molecular Biology Cells Cultured Oligonucleotide Array Sequence Analysis Neurons Reverse Transcriptase Polymerase Chain Reaction Stem Cells Neurogenesis Mechanisms of Signal Transduction Brain Metalloendopeptidases Cell Differentiation Cell Biology Dipeptides Molecular biology Immunohistochemistry Receptor TIE-2 Neural stem cell Recombinant Proteins Neuroepithelial cell Stroke medicine.anatomical_structure Electroporation Stem cell Microdissection |
| Popis: | Ischemic stroke stimulates neurogenesis in the adult rodent brain. The molecules underlying stroke-induced neurogenesis have not been fully investigated. Using real-time reverse transcription-PCR, we found that stroke substantially up-regulated angiopoietin 2 (ANG2), a proangiogenic gene, expression in subventricular zone neural progenitor cells. Incubation of neural progenitor cells with recombinant human ANG2 significantly increased the number of beta-III tubulin-positive cells, a marker of immature neurons, but did not alter the number of glial fibrillary acidic protein (GFAP)-positive cells, a marker of astrocytes, suggesting that ANG2 promotes neuronal differentiation. Blockage of the ANG2 receptor, Tie2, with small interference RNA (siRNA)-Tie2 attenuated recombinant human ANG2 (rhANG2)-increased beta-III tubulin mRNA levels compared with levels in the progenitor cells transfected with control siRNA. Chromatin immunoprecipitation analysis revealed that CCAAT/enhancer-binding protein (C/EBP beta) up-regulated by rhANG2 bound to beta-III tubulin, which is consistent with published data that there are several C/EBP beta binding sites in the promoter of beta-III tubulin gene. In addition, rhANG2 enhanced migration of neural progenitor cells measured by single neurosphere assay. Blockage of Tie2 with siRNA-Tie2 and a Tie2-neutralizing antibody did not suppress ANG2-enhanced migration. However, inhibition of matrix metalloproteinases with GM6001 blocked ANG2-enhanced migration. Collectively, our data suggest that interaction of ANG2, a proangiogenic factor, with its receptor Tie2 promotes neural progenitor cell differentiation into neuronal lineage cells, whereas ANG2 regulates neural progenitor cell migration through matrix metalloproteinases, which do not require its receptor Tie2. |
| Databáze: | OpenAIRE |
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