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J Cell Physiol. 2019 Jul;234(7):11240-11246. doi: 10.1002/jcp.27778. Epub 2018 Dec 10.

Induction of CRMP-2 phosphorylation by CDK5 restricts the repair of damaged optic nerve.

Author information

1
Department of Ophthalmology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
2
Department of Ophthalmology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.

Abstract

OBJECTIVE:

To study the mechanism of collapsin response mediator protein-2 (CRMP-2) phosphorylation changes and cyclin-dependent kinase 5 (CDK5) expression after optic nerve injury.

METHODS:

Optic nerve injury rat models were constructed, the messenger RNA (mRNA) level of CRMP-2 in optic nerve tissues was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) after building models 0, 3, 7, and 14 days. The protein expression of CRMP-2, phospho-CRMP-2 (p-CRMP-2), and CDK5 were also determined by western blot analysis. Lentivirus overexpressing CRMP-2 and CRMP-2 small interfering RNA (siRNA) plasmid were designed and transfected to retina ganglion cells (RGCs), and then the neurites outgrowth of RGCs were cultured with CDK5 inhibitor or CDK5 activator was determined by tubulin staining. Inhibition on CDK5 promotes injured optic nerve by using carrying CDK5 siRNA inject into vitreous chamber.

RESULTS:

There was no significant change in CRMP-2 expression in optic nerve injury rat, while p-CRMP-2 expression was evidently increased compared with sham operation group. The expression level of CDK5 in optic nerve tissue was upregulated after optic nerve injury in rat, and the upward trend of p-CRMP-2 and CDK5 was consistent with the time after the injury was prolonged. Inhibition on CDK5 evidently decreased the expression of p-CRMP-2. CDK5 siRNA had an obvious repair effect on the injured optic nerve.

CONCLUSION:

The increase of CDK5 activity can lead to CRMP-2 hyperphosphorylation, which results in the difficult repair of damaged optic nerve. Therefore, inhibition on CDK5 could promote the repair of damaged optic nerve.

KEYWORDS:

CDK5; CRMP-2; optic nerve; phosphorylation

PMID:
30537069
DOI:
10.1002/jcp.27778

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