MicroRNAs in the axon locally mediate the effects of chondroitin sulfate proteoglycans and cGMP on axonal growth

Document Type

Article

Publication Date

12-1-2015

Publication Title

Dev Neurobiol

Abstract

Axonal miRNAs locally regulate axonal growth by modulating local protein composition. Whether localized miRNAs in the axon mediate the inhibitory effect of Chondroitin sulfate proteoglycans (CSPGs) on the axon remains unknown. We showed that in cultured cortical neurons, axonal application of CSPGs inhibited axonal growth and altered axonal miRNA profiles, whereas elevation of axonal cyclic guanosine monophosphate (cGMP) levels by axonal application of sildenafil reversed the effect of CSPGs on inhibition of axonal growth and on miRNA profiles. Specifically, CSPGs elevated and reduced axonal levels of miR-29c and integrin β1 (ITGB1) proteins, respectively, while elevation of cGMP levels overcame these CSPG effects. Gain-of- and loss-of-function experiments demonstrated that miR-29c in the distal axon mediates axonal growth downstream of CSPGs and cGMP by regulating axonal protein levels of ITGB1, FAK, and RhoA. Together, our data demonstrate that axonal miRNAs play an important role in mediating the inhibitory action of CSPGs on axonal growth and that miR-29c at least partially mediates this process.

Medical Subject Headings

Animals; Axons; Cell Enlargement; Cells, Cultured; Cerebral Cortex; Chondroitin Sulfate Proteoglycans; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Focal Adhesion Kinase 1; HEK293 Cells; Humans; MicroRNAs; Phosphodiesterase 5 Inhibitors; RNA, Messenger; Rats, Wistar; Sildenafil Citrate

PubMed ID

25788427

Volume

75

Issue

12

First Page

1402

Last Page

1419

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