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| Content Provider | Directory of Open Access Journals (DOAJ) |
|---|---|
| Author | Liuliu Pan Hilary A. North Vibhu Sahni Su Ji Jeong Tammy L. Mcguire Eric J. Berns Samuel I. Stupp John A. Kessler |
| Abstract | Astrogliosis with glial scar formation after damage to the nervous system is a major impediment to axonal regeneration and functional recovery. The present study examined the role of β1-integrin signaling in regulating astrocytic differentiation of neural stem cells. In the adult spinal cord β1-integrin is expressed predominantly in the ependymal region where ependymal stem cells (ESCs) reside. β1-integrin signaling suppressed astrocytic differentiation of both cultured ESCs and subventricular zone (SVZ) progenitor cells. Conditional knockout of β1-integrin enhanced astrogliogenesis both by cultured ESCs and by SVZ progenitor cells. Previous studies have shown that injection into the injured spinal cord of a self-assembling peptide amphiphile that displays an IKVAV epitope (IKVAV-PA) limits glial scar formation and enhances functional recovery. Here we find that injection of IKVAV-PA induced high levels of β1-integrin in ESCs in vivo, and that conditional knockout of β1-integrin abolished the astroglial suppressive effects of IKVAV-PA in vitro. Injection into an injured spinal cord of PAs expressing two other epitopes known to interact with β1-integrin, a Tenascin C epitope and the fibronectin epitope RGD, improved functional recovery comparable to the effects of IKVAV-PA. Finally we found that the effects of β1-integrin signaling on astrogliosis are mediated by integrin linked kinase (ILK). These observations demonstrate an important role for β1-integrin/ILK signaling in regulating astrogliosis from ESCs and suggest ILK as a potential target for limiting glial scar formation after nervous system injury. |
| e-ISSN | 19326203 |
| DOI | 10.1371/journal.pone.0104335 |
| Journal | PLoS ONE |
| Issue Number | 8 |
| Volume Number | 9 |
| Language | English |
| Publisher | Public Library of Science (PLoS) |
| Publisher Date | 2014-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Medicine Science |
| Content Type | Text |
| Resource Type | Article |
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