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The NFATC2/Nrf2 cascade regulates spinal cord ischemia-reperfusion injury by controlling inflammation, apoptosis and

Kunbin Li1, Liming Lu2, Xianli Yao1

  • 1Department of Neurorehabilitation, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China.

Regenerative Therapy
|December 25, 2024
PubMed

Insights

The NFATC2/Nrf2 pathway regulates spinal cord ischemia/reperfusion (SCII) injury by controlling inflammation, apoptosis, and oxidative stress. NFATC2 activates Nrf2, offering a potential therapeutic target for SCII.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pathology

Background:

  • Spinal cord ischemia/reperfusion (SCII) injury causes significant neurological deficits.
  • Nuclear factor erythroid 2-related factor 2 (Nrf2) upregulation shows promise in mitigating SCII.
  • Identifying upstream regulators of Nrf2 in SCII is crucial for therapeutic development.

Purpose of the Study:

  • To identify a transcription factor that enhances Nrf2 expression in the context of SCII.
  • To elucidate the regulatory mechanism of this transcription factor on Nrf2.
  • To evaluate the therapeutic potential of the identified pathway in SCII models.

Main Methods:

  • Established *in vitro* (PC12 cells with oxygen-glucose deprivation/reoxygenation) and *in vivo* (rat SCII model) injury models.
  • Assessed cell viability, apoptosis, inflammation (IL-1β, TNF-α), and oxidative stress (ROS, MDA, SOD, GSH-Px).
  • Utilized bioinformatic analysis, chromatin immunoprecipitation (ChIP), and luciferase reporter assays to validate the NFATC2/Nrf2 interaction.

Main Results:

  • Nrf2 and NFATC2 levels were decreased in SCII models.
  • Increased Nrf2 expression significantly reduced inflammation, apoptosis, and oxidative stress in both *in vitro* and *in vivo* models.
  • NFATC2 was identified as a transcription factor that activates Nrf2 expression.
  • Reduced Nrf2 counteracted the protective effects of NFATC2.

Conclusions:

  • The NFATC2/Nrf2 signaling pathway plays a critical role in regulating inflammation, apoptosis, and oxidative stress following SCII.
  • NFATC2 acts as a positive regulator of Nrf2 transcription in SCII.
  • Targeting the NFATC2/Nrf2 cascade presents a promising therapeutic strategy for SCII.
Keywords:
InflammationNrf2Oxidative stressSpinal cord ischemia/reperfusion (IR) injuryTranscription factor

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