Chondroitin Sulfate Impairs Neural Stem Cell Migration Through ROCK Activation.
Layla T GalindoMayara T V V MundimAgnes S PintoGabrielly M D ChiarantinMaíra E S AlmeidaMarcelo L LamersAlan R HorwitzMarinilce F SantosMarimelia Aparecida PorcionattoPublished in: Molecular neurobiology (2017)
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.
Keyphrases
- cell migration
- extracellular matrix
- signaling pathway
- neural stem cells
- hyaluronic acid
- spinal cord injury
- atrial fibrillation
- neuropathic pain
- single cell
- stem cells
- pi k akt
- diabetic rats
- white matter
- oxidative stress
- escherichia coli
- cerebral ischemia
- cystic fibrosis
- staphylococcus aureus
- cell proliferation
- subarachnoid hemorrhage
- induced apoptosis
- resting state
- drug induced