Functional requirement of dicer1 and miR-17-5p in reactive astrocyte proliferation after spinal cord injury in the mouse

Peiwei Hong, Mei Jiang, Hedong Li

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Reactive astrogliosis after spinal cord injury (SCI) contributes to glial scar formation that impedes axonal regeneration. The mechanisms underlying reactive astrocyte proliferation upon injury remain partially understood. MicroRNAs (miRNAs) function as a major class of post-transcriptional gene expression regulators that participate in many biological processes. However, miRNA function during reactive astrogliosis, particularly in injury-induced astrocyte proliferation, has not been carefully examined. In this study, we conditionally deleted Dicer1 gene encoding an enzyme that is required for mature miRNA generation, and examined the proliferative behavior of Dicer1-null reactive astrocytes in the transected mouse spinal cord. We found that injury-induced proliferation is blocked in Dicer1-null astrocytes. Previous reports indicate that miR-17-5p family members are upregulated during SCI. We therefore tested functional contribution of miR-17-5p to the proliferation of reactive astrocytes in vitro. Our results showed that a synthetic miR-17-5p mimic is able to rescue the proliferation defect of Dicer1-null astrocytes, while an antisense inhibitor of miR-17-5p blocked lipopolysaccharide-induced astrocytic proliferation. Similar results are also observed in leukemia inhibitory factor (LIF)-treated astroglial cultures suggesting that miR-17-5p particularly modulates reactive astrocyte proliferation initiated by LIF presumably via the JAK/STAT3 pathway. Furthermore, overexpression of miR-17-5p leads to decrease of several cell cycle regulators in cultured astroglia and astrocytoma cell line C6. Our conclusion is that miRNAs are indispensable to the injury-induced reactive astrocyte proliferation, and that miR-17-5p may be a major player regulating this pathological process by affecting cell cycle machinery.

Original languageEnglish (US)
Pages (from-to)2044-2060
Number of pages17
JournalGlia
Volume62
Issue number12
DOIs
StatePublished - Dec 1 2014
Externally publishedYes

Keywords

  • Dicer (Dicer1)
  • MiR-17-5p
  • MiRNAs
  • Proliferation
  • Spinal cord injury

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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