Chondroitin Sulfate Impairs Neural Stem Cell Migration Through ROCK Activation
Brain injuries such as trauma and stroke lead to glial scar formation by reactive astrocytes which produce and secret axonal outgrowth inhibitors. Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of extracellular matrix molecules produced at the glial scar and cause growth cone...
| Authors: | , , , , , , , , |
|---|---|
| Format: | article |
| Status: | Published version |
| Publication Date: | 2018 |
| Country: | Brasil |
| Institution: | Universidade Federal do Rio Grande do Sul (UFRGS) |
| Repository: | Repositório Institucional da UFRGS |
| Language: | English |
| OAI Identifier: | oai:www.lume.ufrgs.br:10183/263607 |
| Online Access: | http://hdl.handle.net/10183/263607 |
| Access Level: | Open access |
| Keyword: | Células tronco neurais Movimento celular Sulfatos de condroitina Lesões encefálicas traumáticas Proteína rhoA de Ligação ao GTP Neural stem cell Cell migration Chondroitin sulfate Traumatic brain injury RhoA Rock |
| Summary: | Brain injuries such as trauma and stroke lead to glial scar formation by reactive astrocytes which produce and secret axonal outgrowth inhibitors. Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of extracellular matrix molecules produced at the glial scar and cause growth cone collapse. The CSPG glycosaminoglycan side chains composed of chondroitin sulfate (CS) are responsible for its inhibitory activity on neurite outgrowth and are dependent on RhoA activation. Here, we hypothesize that CSPG also impairs neural stem cell migration inhibiting their penetration into an injury site. We show that DCX+ neuroblasts do not penetrate a CSPG-rich injured area probably due to Nogo receptor activation and RhoA/ROCK signaling pathway as we demonstrate in vitro with neural stem cells cultured as neurospheres and pull-down for RhoA. Furthermore, CS-impaired cell migration in vitro induced the formation of large mature adhesions and altered cell protrusion dynamics. ROCK inhibition restored migration in vitro as well as decreased adhesion size. |
|---|