title: β1-Integrin and integrin linked kinase regulate astrocytic differentiation of neural stem cells.
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.
authors.affiliation: Department of Neurology, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Liuliu
authors.initials: L
authors.lastname: Pan
authors.affiliation: Department of Neurology, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Hilary A
authors.initials: HA
authors.lastname: North
authors.affiliation: Department of Neurology, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Vibhu
authors.initials: V
authors.lastname: Sahni
authors.affiliation: Department of Neurology, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Su Ji
authors.initials: SJ
authors.lastname: Jeong
authors.affiliation: Department of Neurology, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Tammy L
authors.initials: TL
authors.lastname: Mcguire
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Berns
authors.affiliation: Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois, United States of America; Department of Chemistry, Northwestern University, Evanston, Illinois, United States of America; Department of Medicine and Institute for BioNanotechnology in Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Stupp
authors.affiliation: Department of Neurology, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: John A
authors.initials: JA
authors.lastname: Kessler
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D000939:Epitopes / Q000494:pharmacology; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000494:pharmacology; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000099200:Scaffold Protein ILK
chemical_list: D000939:Epitopes; D019012:Integrin beta1; D007797:Laminin; D009842:Oligopeptides; D010446:Peptide Fragments; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK; C083321:isoleucyl-lysyl-valyl-alanyl-valine; C047981:arginyl-glycyl-aspartic acid
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