β1-integrin and integrin linked kinase regulate astrocytic differentiation of neural stem cells

Liuliu Pan, Hilary A. North, Vibhu Sahni, Su Ji Jeong, Tammy L. Mcguire, Eric J. Berns, Samuel I. Stupp, John A. Kessler

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41 Citations (Scopus)

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.

Original languageEnglish
Article numbere104335
JournalPLoS ONE
Volume9
Issue number8
DOIs
Publication statusPublished - Aug 6 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Pan, L., North, H. A., Sahni, V., Jeong, S. J., Mcguire, T. L., Berns, E. J., Stupp, S. I., & Kessler, J. A. (2014). β1-integrin and integrin linked kinase regulate astrocytic differentiation of neural stem cells. PLoS ONE, 9(8), [e104335]. https://doi.org/10.1371/journal.pone.0104335