Silencing miR-21 Induces Polarization of Astrocytes to the A2 Phenotype and Improves the Formation of Synapses by Targeting gpc6 via the STAT3 Pathway After Acute Ischemic Spinal Cord Injury

Abstract

Background: Ischemic spinal cord injury (ISCI) results in the motor sensory dysfunction of the limbs below the injury site. In response to the injury, astrocytes develop into neuroprotective astrocytes (A2s) to mitigate the damage. Methods: We used the abdominal aortic occlusion model in vivo. Immunohistochemistry was used to detect the distribution of A2s in the spinal cord. We used an Oxygen Glucose Deprivation(OGD) method to model astrocytes ischemia in vitro, and tested proliferation, migration, and excitability of A2 astrocytes using an Edu, wound scratch assay, and a calcium-ion probe. After adjustment miR-21, we detected the model and target genes of A2s using polymerase chain reaction, Western blot, immunofluorescence, and chromatin immunoprecipitation. Findings: These results showed that miR-21 could regulate the conversion between A1s and A2s and that A2s mediated synapsis by targeting gpc6 and neurite growth by means of gdnf via the STAT3 pathway. Interpretation: miR-21 is a switch to regulate the polarization of reactive astrocyte, and promoted synapsis formation and nerites growth after acute ISCI. Funding Statement: Grant support was provided by the National Natural Science Funds of China (Nos. 81401014, 81771346), the Chinese Postdoctoral Science Foundation (No. 2014M561935), and the Chinese Postdoctoral Science Foundation (No. 2015T80725), Technology Research and Development Program of Jinan City(No. 201704133). Declaration of Interests: All authors: No reported conflicts. Ethics Approval Statement: All procedures were performed in accordance with the animal care standards of the Chinese National Institute of Health(CNIH) and regulations of the Taishan medical university Committee for the Care and Use of Laboratory Animals.