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MicroRNA-299a-5p Protects against Spinal Cord Injury through Activating AMPK Pathway

Zong-Ze Zhang1, Shu-Yue Xian1, Chong Bao1

  • 1Department of Anesthesiology, Zhongnan Hospital of Wuhan University, China.

Oxidative Medicine and Cellular Longevity
|May 23, 2022
PubMed
Abstract

Insights

MicroRNA-299a-5p (miR-299a-5p) protects against spinal cord injury (SCI) by reducing inflammation and oxidative stress. This study reveals miR-299a-5p activates the AMP-activated protein kinase (AMPK) pathway, offering a potential therapeutic target for SCI.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Spinal cord injury (SCI) involves inflammation and oxidative stress.
  • The role of microRNA-299a-5p (miR-299a-5p) in SCI pathogenesis is not well understood.

Purpose of the Study:

  • To investigate the function and molecular mechanisms of miR-299a-5p in mouse models of SCI.
  • To explore the potential of miR-299a-5p as a therapeutic agent for SCI.

Main Methods:

  • Mice underwent SCI surgery and received intrathecal injections of miR-299a-5p agomir or antagomir.
  • AMP-activated protein kinase (AMPK) was inhibited using compound C or genetic methods.
  • pH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1) was overexpressed using lentiviral vectors.

Main Results:

  • SCI significantly reduced miR-299a-5p expression in the spinal cord.
  • miR-299a-5p overexpression protected against SCI, while inhibition exacerbated it.
  • miR-299a-5p directly inhibited PHLPP1, leading to AMPK activation.
  • PHLPP1 overexpression or AMPK inhibition abolished the protective effects of miR-299a-5p.

Conclusions:

  • miR-299a-5p exerts protective effects against SCI.
  • The protective mechanism involves the inhibition of PHLPP1 and subsequent activation of the AMPK pathway.
  • miR-299a-5p represents a potential therapeutic target for managing SCI.

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