| First Author | North HA | Year | 2015 |
| Journal | J Neurosci | Volume | 35 |
| Issue | 9 | Pages | 3725-33 |
| PubMed ID | 25740503 | Mgi Jnum | J:219937 |
| Mgi Id | MGI:5630002 | Doi | 10.1523/JNEUROSCI.4546-14.2015 |
| Citation | North HA, et al. (2015) beta1-Integrin Alters Ependymal Stem Cell BMP Receptor Localization and Attenuates Astrogliosis after Spinal Cord Injury. J Neurosci 35(9):3725-33 |
| abstractText | Astrogliosis after spinal cord injury (SCI) is a major impediment to functional recovery. More than half of new astrocytes generated after SCI are derived from ependymal zone stem cells (EZCs). We demonstrate that expression of beta1-integrin increases in EZCs following SCI in mice. Conditional knock-out of beta1-integrin increases GFAP expression and astrocytic differentiation by cultured EZCs without altering oligodendroglial or neuronal differentiation. Ablation of beta1-integrin from EZCs in vivo reduced the number of EZC progeny that continued to express stem cell markers after SCI, increased the proportion of EZC progeny that differentiated into GFAP+ astrocytes, and diminished functional recovery. Loss of beta1-integrin increased SMAD1/5/8 and p38 signaling, suggesting activation of BMP signaling. Coimmunoprecipitation studies demonstrated that beta1-integrin directly interacts with the bone morphogenetic protein receptor subunits BMPR1a and BMPR1b. Ablation of beta1-integrin reduced overall levels of BMP receptors but significantly increased partitioning of BMPR1b into lipid rafts with increased SMAD1/5/8 and p38 signaling. Thus beta1-integrin expression by EZCs reduces movement of BMPR1b into lipid rafts, thereby limiting the known deleterious effects of BMPR1b signaling on glial scar formation after SCI. |
