Downregulation of thymosin beta4 in neural progenitor grafts promotes spinal cord regeneration
| Autor: | Enrico Garaci, Lucia Ricci-Vitiani, Daniela Merlo, Corrado Lucantoni, Anna Maria Rinaldi, Mauro Racaniello, Cristina Zona, Roberto Pallini, Ruggero De Maria, Cristiana Mollinari, Massimo Pieri |
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| Rok vydání: | 2009 |
| Předmět: |
Telencephalon
Neurite Neurogenesis Down-Regulation Neural Cell Adhesion Molecule L1 Spinal cord injury Cell Communication Biology Settore BIO/09 DNA Antisense Thymosin β4 Animals beta Catenin Disease Models Animal Mice Cadherins Spinal Cord Injuries Nerve Regeneration Neurons Thymosin Axons Stem Cells Stem Cell Transplantation Downregulation and upregulation Settore MED/04 - PATOLOGIA GENERALE medicine Antisense Spinal Cord Regeneration Progenitor Cell adhesion molecule Animal Neurite outgrowth DNA Cell Biology Spinal cord Adhesion molecules Neural progenitor cell graft Neuronal differentiation Neural stem cell Cell biology medicine.anatomical_structure Immunology Disease Models Thymosin beta 4 neuronal differentiation |
| Zdroj: | Journal of cell science 122 (2009): 4195–4207. doi:10.1242/jcs.056895 info:cnr-pdr/source/autori:Mollinari, C1; Ricci-Vitiani, L2; Pieri, M3,4; Lucantoni, C5; Rinaldi, AM3; Racaniello, M3,6; De Maria, R2; Zona, C3,4; Pallini, R5; Merlo, D1,6; Garaci, E7/titolo:Downregulation of thymosin beta4 in neural progenitor grafts promotes spinal cord regeneration/doi:10.1242%2Fjcs.056895/rivista:Journal of cell science/anno:2009/pagina_da:4195/pagina_a:4207/intervallo_pagine:4195–4207/volume:122 |
| ISSN: | 1477-9137 |
| DOI: | 10.1242/jcs.056895 |
| Popis: | Thymosin beta4 (Tbeta4) is an actin-binding peptide whose expression in developing brain correlates with migration and neurite extension of neurons. Here, we studied the effects of the downregulation of Tbeta4 expression on growth and differentiation of murine neural progenitor cells (NPCs), using an antisense lentiviral vector. In differentiation-promoting medium, we found twice the number of neurons derived from the Tbeta4-antisense-transduced NPCs, which showed enhanced neurite outgrowth accompanied by increased expression of the adhesion complex N-cadherin-beta-catenin and increased ERK activation. Importantly, when the Tbeta4-antisense-transduced NPCs were transplanted in vivo into a mouse model of spinal cord injury, they promoted a significantly greater functional recovery. Locomotory recovery correlated with increased expression of the regeneration-promoting cell adhesion molecule L1 by the grafted Tbeta4-antisense-transduced NPCs. This resulted in an increased number of regenerating axons and in sprouting of serotonergic fibers surrounding and contacting the Tbeta4-antisense-transduced NPCs grafted into the lesion site. In conclusion, our data identify a new role for Tbeta4 in neuronal differentiation of NPCs by regulating fate determination and process outgrowth. Moreover, NPCs with reduced Tbeta4 levels generate an L1-enriched environment in the lesioned spinal cord that favors growth and sprouting of spared host axons and enhances the endogenous tissue-repair processes. |
| Databáze: | OpenAIRE |
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