MiR-429 regulates blood−spinal cord barrier permeability by targeting Krüppel-like factor 6

• DOI: 10.1016/j.bbrc.2020.02.138
• Publication Date: 2020-03-09T02:09:46Z
• Authors: Rui Sun; Lihao Ge; Yang Cao; Wenmao Wu; Yu Wu; Honggang Zhu; Jiuwei Li; Deshui Yu
• Keywords: 0303 health sciences; Tight Junction Proteins; Green Fluorescent Proteins; Models, Biological; Permeability; Cell Line; MicroRNAs; 03 medical and health sciences; Blood; Gene Expression Regulation; Spinal Cord; Kruppel-Like Factor 6; Humans

The blood-spinal cord barrier (BSCB) is an effective, tightly-connected tissue that reduces secondary spinal cord injury (SCI) by decreasing blood cell infiltration, inflammation, and neuronal cell death during primary SCI. However, the methods and molecular mechanisms of BSCB openness remain elusive. In the present study, we found that microRNA429 (miR-429) plays a vital role in the opening of the blood-spinal cord. Inhibiting the expression of miR-429 (antagomiR-429) resulted in increased expression levels of the tight junction (TJ) proteins, ZO-1, occludin, and claudin-5, in the BSCB and reduced BSCB permeability. Moreover, overexpression of miR-429 (agomiR-429) had the opposite effect. Krüppel-like factor 6 (KLF6) is a transcription factor of the zinc-finger family. Using RT-qPCR and western blotting, we found that miR-429 can negatively regulate the expression of the KLF6. Co-transfection of KLF6 and miR-429 demonstrated that miR-429 negatively regulates KLF6 to mediate TJ protein expression and BSCB permeability. Based on these results, we suggest that KLF6 may be a downstream target of miR-429, mediating TJ protein expression to regulate the BSCB.