β1-Integrin and integrin linked kinase regulate astrocytic differentiation of neural stem cells.
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-inte...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4123915?pdf=render |
| _version_ | 1828825781815476224 |
|---|---|
| author | Liuliu Pan Hilary A North Vibhu Sahni Su Ji Jeong Tammy L Mcguire Eric J Berns Samuel I Stupp John A Kessler |
| author_facet | Liuliu Pan Hilary A North Vibhu Sahni Su Ji Jeong Tammy L Mcguire Eric J Berns Samuel I Stupp John A Kessler |
| author_sort | Liuliu Pan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T14:25:33Z |
| format | Article |
| id | doaj.art-77810a875a8b49d7aa16c51a273f1c98 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T14:25:33Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-77810a875a8b49d7aa16c51a273f1c982022-12-22T00:21:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10433510.1371/journal.pone.0104335β1-Integrin and integrin linked kinase regulate astrocytic differentiation of neural stem cells.Liuliu PanHilary A NorthVibhu SahniSu Ji JeongTammy L McguireEric J BernsSamuel I StuppJohn A KesslerAstrogliosis 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.http://europepmc.org/articles/PMC4123915?pdf=render |
| spellingShingle | Liuliu Pan Hilary A North Vibhu Sahni Su Ji Jeong Tammy L Mcguire Eric J Berns Samuel I Stupp John A Kessler β1-Integrin and integrin linked kinase regulate astrocytic differentiation of neural stem cells. PLoS ONE |
| title | β1-Integrin and integrin linked kinase regulate astrocytic differentiation of neural stem cells. |
| title_full | β1-Integrin and integrin linked kinase regulate astrocytic differentiation of neural stem cells. |
| title_fullStr | β1-Integrin and integrin linked kinase regulate astrocytic differentiation of neural stem cells. |
| title_full_unstemmed | β1-Integrin and integrin linked kinase regulate astrocytic differentiation of neural stem cells. |
| title_short | β1-Integrin and integrin linked kinase regulate astrocytic differentiation of neural stem cells. |
| title_sort | β1 integrin and integrin linked kinase regulate astrocytic differentiation of neural stem cells |
| url | http://europepmc.org/articles/PMC4123915?pdf=render |
| work_keys_str_mv | AT liuliupan b1integrinandintegrinlinkedkinaseregulateastrocyticdifferentiationofneuralstemcells AT hilaryanorth b1integrinandintegrinlinkedkinaseregulateastrocyticdifferentiationofneuralstemcells AT vibhusahni b1integrinandintegrinlinkedkinaseregulateastrocyticdifferentiationofneuralstemcells AT sujijeong b1integrinandintegrinlinkedkinaseregulateastrocyticdifferentiationofneuralstemcells AT tammylmcguire b1integrinandintegrinlinkedkinaseregulateastrocyticdifferentiationofneuralstemcells AT ericjberns b1integrinandintegrinlinkedkinaseregulateastrocyticdifferentiationofneuralstemcells AT samuelistupp b1integrinandintegrinlinkedkinaseregulateastrocyticdifferentiationofneuralstemcells AT johnakessler b1integrinandintegrinlinkedkinaseregulateastrocyticdifferentiationofneuralstemcells |