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- Title
β1-Integrin Alters Ependymal Stem Cell BMP Receptor Localization and Attenuates Astrogliosis after Spinal Cord Injury.
- Authors
North, Hilary A.; Pan, Liuliu; McGuire, Tammy L.; Brooker, Sarah; Kessler, John A.
- 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 β1-integrin increases in EZCs following SCI in mice. Conditional knock-out of β1-integrin increases GFAP expression and astrocytic differentiation by cultured EZCs without altering oligodendroglial or neuronal differentiation. Ablation of β1-integrin from EZCs in vivo reduced the number of EZC progeny that continued to express stem cell markers after SCI, increased the proportion of EZCprogeny that differentiated into GFAP + astrocytes, and diminished functional recovery. Loss of β1-integrin increased SMAD1/5/8 and p38 signaling, suggesting activation of BMP signaling. Coimmunoprecipitation studies demonstrated that β1-integrin directly interacts with the bone morphogenetic protein receptor subunits BMPR1a and BMPR1b. Ablation of β1-integrin reduced overall levels of BMP receptors but significantly increased partitioning of BMPRib into lipid rafts with increased SMAD1/5/8 and p38 signaling. Thus β1-integrin expression by EZCs reduces movement of BMPRib into lipid rafts, thereby limiting the known deleterious effects of BMPRib signaling on glial scar formation after SCI.
- Subjects
GLIOSIS; SPINAL cord injuries; INTEGRIN genetics; LABORATORY mice; NEURAL stem cells; BONE morphogenetic proteins
- Publication
Journal of Neuroscience, 2015, Vol 35, Issue 9, p3725
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.4546-14.2015