title: MicroRNAs in the axon locally mediate the effects of chondroitin sulfate proteoglycans and cGMP on axonal growth.
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.
authors: Department of Neurology, Henry Ford Hospital, Detroit, Michigan, 48202.
authors: Yi
authors: Y
authors: Zhang
authors: Department of Neurology, Henry Ford Hospital, Detroit, Michigan, 48202.|Department of Physics, Oakland University, Rochester, Michigan, 48309.
authors: Michael
authors: M
authors: Chopp
authors: Department of Neurology, Henry Ford Hospital, Detroit, Michigan, 48202.
authors: Xian Shuang
authors: XS
authors: Liu
authors: Department of Neurology, Henry Ford Hospital, Detroit, Michigan, 48202.
authors: Haifa
authors: H
authors: Kassis
authors: Department of Neurology, Henry Ford Hospital, Detroit, Michigan, 48202.
authors: Xinli
authors: X
authors: Wang
authors: Department of Neurology, Henry Ford Hospital, Detroit, Michigan, 48202.
authors: Chao
authors: C
authors: Li
authors: International Academy, Troy, Michigan, 48083.
authors: Guangning
authors: G
authors: An
authors: Department of Neurology, Henry Ford Hospital, Detroit, Michigan, 48202.
authors: Zheng Gang
authors: ZG
authors: Zhang
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D049108:Cell Enlargement / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D000068677:Sildenafil Citrate / Q000494:pharmacology
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D035683:MicroRNAs; D058986:Phosphodiesterase 5 Inhibitors; D012333:RNA, Messenger; D000068677:Sildenafil Citrate; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006152:Cyclic GMP
keywords: axon growth; cGMP; chondroitin sulfate proteoglycans; miRNA