ß1-Integrin alters ependymal stem cell BMP receptor localization and attenuates astrogliosis after spinal cord injury.
J Neurosci
; 35(9): 3725-33, 2015 Mar 04.
Article
em En
| MEDLINE
| ID: mdl-25740503
ABSTRACT
Astrogliosis after spinal cord injury (SCI) is a major impediment to functional recovery. More than half of new astrocytes generated after SCI are derived from ependymal zone stem cells (EZCs). We demonstrate that expression of ß1-integrin increases in EZCs following SCI in mice. Conditional knock-out of ß1-integrin increases GFAP expression and astrocytic differentiation by cultured EZCs without altering oligodendroglial or neuronal differentiation. Ablation of ß1-integrin from EZCs in vivo reduced the number of EZC progeny that continued to express stem cell markers after SCI, increased the proportion of EZC progeny that differentiated into GFAP+ astrocytes, and diminished functional recovery. Loss of ß1-integrin increased SMAD1/5/8 and p38 signaling, suggesting activation of BMP signaling. Coimmunoprecipitation studies demonstrated that ß1-integrin directly interacts with the bone morphogenetic protein receptor subunits BMPR1a and BMPR1b. Ablation of ß1-integrin reduced overall levels of BMP receptors but significantly increased partitioning of BMPR1b into lipid rafts with increased SMAD1/5/8 and p38 signaling. Thus ß1-integrin expression by EZCs reduces movement of BMPR1b into lipid rafts, thereby limiting the known deleterious effects of BMPR1b signaling on glial scar formation after SCI.
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Base de dados:
MEDLINE
Assunto principal:
Traumatismos da Medula Espinal
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Astrócitos
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Integrina beta1
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Epêndima
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Receptores de Proteínas Morfogenéticas Ósseas
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Células-Tronco Neurais
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Gliose
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article