beta 1-Integrin and Integrin Linked Kinase Regulate Astrocytic Differentiation of Neural Stem Cells: e104335

• Published in: PloS one Vol. 9; no. 8
• Main Authors: Pan, Liuliu, North, Hilary A, Sahni, Vibhu, Jeong, Su Ji, Mcguire, Tammy L, Berns, Eric J, Stupp, Samuel I, Kessler, John A
• Format: Journal Article
• Language: English
• Published: 01-08-2014
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0104335

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 beta 1-integrin signaling in regulating astrocytic differentiation of neural stem cells. In the adult spinal cord beta 1-integrin is expressed predominantly in the ependymal region where ependymal stem cells (ESCs) reside. beta 1-integrin signaling suppressed astrocytic differentiation of both cultured ESCs and subventricular zone (SVZ) progenitor cells. Conditional knockout of beta 1-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 beta 1-integrin in ESCs in vivo, and that conditional knockout of beta 1-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 beta 1-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 beta 1-integrin signaling on astrogliosis are mediated by integrin linked kinase (ILK). These observations demonstrate an important role for beta 1-integrin/ILK signaling in regulating astrogliosis from ESCs and suggest ILK as a potential target for limiting glial scar formation after nervous system injury.