MicroRNA-9 regulates mammalian axon regeneration in peripheral nerve injury
نویسندگان
چکیده
Abstract Effective axon regeneration is achieved mainly by precise regulation of gene expression after peripheral nerve injury. MicroRNAs play an important role in controlling axon regeneration owe to its key epigenetic function in regulating gene expression. Here, we reveal that microRNA-9 (miR-9) may be a new suppressor of axon regeneration and FoxP1 is the functional target of miR-9. High level of endogenous miR-9 in sensory neurons inhibited axon regeneration in vitro and in vivo. In addition, the regulatory effect of miR-9 was mediated by changes in FoxP1 levels. Full rescuing effect of axon regeneration was achieved by FoxP1 up-regulation. Most importantly, we showed that miR-9-FoxP1 might be a new signaling pathway to regulate mammalian axon regrowth. Moreover, we provided the first evidence that maintaining a higher level of FoxP1 in sensory neurons by the microRNA is necessary for efficient axon regeneration.
منابع مشابه
MicroRNA-138 and SIRT1 form a mutual negative feedback loop to regulate mammalian axon regeneration.
Regulated gene expression determines the intrinsic ability of neurons to extend axons, and loss of such ability is the major reason for the failed axon regeneration in the mature mammalian CNS. MicroRNAs and histone modifications are key epigenetic regulators of gene expression, but their roles in mammalian axon regeneration are not well explored. Here we report microRNA-138 (miR-138) as a nove...
متن کاملLocalization of Epidermal-Type Fatty Acid Binding Protein (E-FABP) in Degeneration and Regeneration of Sciatic Nerve after Crush Injury in Mouse
Purpose:The regeneration of axon and myelin sheet after crush injury of peripheral nerves involves interaction of several types of cells, including Schwann cells, monocyte, macrophage and fibroblast. Among them, haematogenous macrophages invading into the peripheral nervous systein play a major role in myelin uptake during Wallerian degeneration. Materials and Methods: In this study 35 C57/BL6 ...
متن کاملEnhanced rate of nerve regeneration and directional errors after sciatic nerve injury in receptor protein tyrosine phosphatase sigma knock-out mice.
The receptor protein tyrosine phosphatase sigma (PTPsigma) is a member of the mammalian leukocyte common antigen-related (LAR) family. Its expression is developmentally regulated in neuronal tissues. The Drosophila homolog of the mammalian LAR family of phosphatases (DLAR) controls axon guidance during Drosophila embryogenesis. We have demonstrated previously that mice deficient in PTPsigma hav...
متن کاملCELF RNA binding proteins promote axon regeneration in C. elegans and mammals through alternative splicing of Syntaxins
Axon injury triggers dramatic changes in gene expression. While transcriptional regulation of injury-induced gene expression is widely studied, less is known about the roles of RNA binding proteins (RBPs) in post-transcriptional regulation during axon regeneration. In C. elegans the CELF (CUGBP and Etr-3 Like Factor) family RBP UNC-75 is required for axon regeneration. Using crosslinking immuno...
متن کاملGuiding adult Mammalian sensory axons during regeneration.
Misdirection of axons after nerve injury impairs successful regeneration of adult neurons. Investigations of axon guidance in development have provided an understanding of pathfinding, but their relevance to regenerating adult axons is unclear. We investigated adult mammalian axon guidance during regeneration after peripheral nerve injury and focused on the effects of the prototypic guidance mo...
متن کامل