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MicroRNA-124 regulates cell pyroptosis during cerebral ischemia-reperfusion injury by regulating STAT3

Hui Sun1,2, Jing-Jing Li1,2, Zi-Ren Feng1,2

  • 1Department of Clinical Laboratory, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China.

Experimental and Therapeutic Medicine
|November 16, 2020
PubMed

Insights

MicroRNA-124 protects the brain from injury after stroke by reducing cell death pathways. This finding offers a potential new treatment for cerebral ischemia-reperfusion injury (CIRI).

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Cerebral ischemia-reperfusion injury (CIRI) is a critical condition with no effective treatments.
  • MicroRNAs (miRNAs) are implicated in CIRI by regulating pyroptosis, a form of programmed cell death.
  • miRNA-124 has emerged as a key regulator in CIRI, potentially through its interaction with STAT3.

Purpose of the Study:

  • To investigate the role of miRNA-124 in regulating pyroptosis during CIRI.
  • To elucidate the relationship between miRNA-124, STAT3 signaling, and pyroptosis in a CIRI model.
  • To assess the neuroprotective potential of modulating miRNA-124 levels in CIRI.

Main Methods:

  • CIRI was induced using a middle cerebral artery occlusion model in rodents.
  • miRNA-124 levels were manipulated using intracerebroventricular injections of agonists or antagonists.
  • Pyroptosis markers (caspase-1, gasdermin D, IL-18, IL-1β) and STAT3 activation were assessed using molecular and histological techniques.
  • Neurological function and brain tissue damage were evaluated via scoring and TTC staining.

Main Results:

  • Pyroptosis markers and pro-inflammatory cytokines were significantly elevated in CIRI models.
  • miRNA-124 agonist administration attenuated pyroptosis and improved neurological function.
  • miRNA-124 directly targeted and inhibited STAT3 activation, thereby reducing pyroptosis.
  • miRNA-124 antagonist reversed the protective effects observed with the agonist.

Conclusions:

  • miRNA-124 demonstrates significant neuroprotective effects against pyroptosis in CIRI.
  • The protective mechanism involves the targeted inhibition of the STAT3 signaling pathway.
  • Modulating miRNA-124 represents a promising therapeutic strategy for treating CIRI.
Keywords:
STAT3caspase-1cerebral ischemia-reperfusion injurygasdermin Dinterleukin-18interleukin-1βmicroRNA-124pyroptosis

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