MicroRNAs in the Axon Locally Mediate the Effects of Chondroitin Sulfate Proteoglycans and CGMP on Axonal Growth

Overview

Journal Dev Neurobiol

Specialties Biology
Neurology

Date 2015 Mar 20

PMID 25788427

Citations 28

Authors

Yi Zhang

Michael Chopp

Xian Shuang Liu

Haifa Kassis

Xinli Wang

Chao Li

Guangning An

Zheng Gang Zhang

Affiliations

Soon will be listed here.

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.

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