Research on Differentiation of Bone Marrow Stromal Cells (BMSCs) Prompted by MicroRNA-124 and Effect on Inflammatory Reaction of Spinal Cord Injury Nerve Cells

The major feature of spinal cord injury (SCI) was the damage of nervous tissue in spinal cord. The damaged spinal cord was difficult to be repaired and regenerated. MicroRNA-124 could play a role in the repairing and recovering the injured tissue. The BMSCs could participate in repairing the damage. However, the regulatory effect of MicroRNA-124 on BMSCs and the inflammatory response of SCI was still not illustrated. These spinal cord nerve cells were assigned into group of mechanical damage, BMSCs and BMSCs with miR-124 overexpression followed by analysis of proliferation of nerve cells by MTT assay, apoptotic activity, expression of miR-124, GFAP and BDNF by Real time PCR, levels of TNF-α and IL-6 by ELISA as well as MDH and SOD activity. miR-124 mimics transfection significantly promoted BMSCs proliferation and increased ALK activity and the expression of GFAP and BDNF. In conclusion, the proliferation and differentiation of BMSCs could be regulated by miR-124. The inflammation and oxidative stress could be restrained so as to prompt the proliferation and repair of SCI cells and restrain apoptosis, indicating that it might be beneficial to recover the SCI.

MicroRNA-124 Alleviates Retinal Vasoregression via Regulating Microglial Polarization

Microglial activation is implicated in retinal vasoregression of the neurodegenerative ciliopathy-associated disease rat model (i.e., the polycystic kidney disease (PKD) model). microRNA can regulate microglial activation and vascular function, but the effect of microRNA-124 (miR-124) on retinal vasoregression remains unclear. Transgenic PKD and wild-type Sprague Dawley (SD) rats received miR-124 at 8 and 10 weeks of age intravitreally. Retinal glia activation was assessed by immunofluorescent staining and in situ hybridization. Vasoregression and neuroretinal function were evaluated by quantitative retinal morphometry and electroretinography (ERG), respectively. Microglial polarization was determined by immunocytochemistry and qRT-PCR. Microglial motility was examined via transwell migration assays, wound healing assays, and single-cell tracking. Our data showed that miR-124 inhibited glial activation and improved vasoregession, as evidenced by the reduced pericyte loss and decreased acellular capillary formation. In addition, miR-124 improved neuroretinal function. miR-124 shifted microglial polarization in the PKD retina from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype by suppressing TNF-α, IL-1β, CCL2, CCL3, MHC-II, and IFN-γ and upregulating Arg1 and IL-10. miR-124 also decreased microglial motility in the migration assays. The transcriptional factor of C/EBP-α-PU.1 signaling, suppressed by miR-124 both in vivo (PKD retina) and in vitro (microglial cells), could serve as a key regulator in microglial activation and polarization. Our data illustrate that miR-124 regulates microglial activation and polarization. miR-124 inhibits pericyte loss and thereby alleviates vasoregression and ameliorates neurovascular function.