After peripheral nerve injury, the degenerative debris and inflammatory alterations at the injury site may block the elongation of regenerating axons to reach target organs. Tissue plasminogen activator (tPA), a serine protease, has a capability of degrading matrix molecules and cell adhesions. In this study, we found that either tPA or miR-340 was differentially expressed in the injured nerve after sciatic nerve injury, and that the expressions of tPA and miR-340 were negatively correlated to each other. Moreover, miR-340 and tPA were co-localized in sciatic nerve. miR-340 regulated tPA through direct targeting of the 3'-UTR of tPA. Functionally, over- or under-expression of miR-340 reduced or augmented the fibrinolytic activity and migration ability of cultured Schwann cells as well as tPA secretion from the cells, respectively. In rats with sciatic nerve crush injury, dysregulation of the miR-340 expression in the injury site affected the cell debris removal and axonal regrowth. Obviously, unlike many previous studies that investigate the functional impact of miRNAs on peripheral nerve regeneration in the perspective of miRNA regulation of neural cell behaviors, the present study focused on miRNA regulation of debris clearance, thus updating our understanding of the regulatory roles of miRNAs in peripheral nerve regeneration.
Keywords: Axon growth; Debris clearance; Fibrinolysis; miR-340; tPA.