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Publications

Journal Article Epublish

PubMed: 40896587 DOI: 10.1016/j.omtn.2025.102670

Context dependent role of miR-486 promoting neuroregeneration of primary sensory neurons downstream of interleukin-6 signal transducer.

Mol Ther Nucleic Acids 36(3):102670

Authors: Theodora Kalpachidou, Kai Kummer, Valentina Handle, David Zimmermann, Maria Peteinareli, Serena Quarta, Natalia Mach, Laura Castaldi, Paul A Heppenstall, Rainer V Haberberger, Hermona Soreq, Michaela Kress

Affiliations

  • Institute of Physiology, Medical University of Innsbruck, Schöpfstrasse 41, Innsbruck 6020, Austria.
  • Health University of Applied Sciences Tyrol / FH Gesundheit Tirol, Innrain 98, Innsbruck 6020, Austria.
  • Epigenetics and Neurobiology Unit, EMBL Rome, Via Ramarini 32, Monterotondo 00015, Italy.
  • Neuroscience Area, International School for Advanced Studies (SISSA/ISAS), Via Bonomea 265, Trieste 34136, Italy.
  • Department of Anatomy and Pathology, School of Biomedicine, The University of Adelaide, Adelaide, SA 5005, Australia.
  • The Alexander Silberman Institute of Life Sciences, the Edmond and Lily Safra Center for Brain Sciences, and Department of Biological Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 9190401, Israel.

Abstract

The pro-inflammatory cytokine interleukin-6 (IL-6) via its IL-6 signal transducer (IL6ST/gp130) plays an important role in neuronal survival, neuro-regeneration, and pathological pain. While its critical importance in the nervous system is well established, the underlying molecular mechanisms and the involvement of microRNAs (miRNAs) as critical regulators of biological processes in health and disease are not sufficiently understood. We identified miR-486-5p as the single significantly deregulated miRNA in sensory neurons with a conditional depletion of gp130. In situ hybridization and immunofluorescence in dorsal root ganglia (DRG) localized miR-486 to small diameter neurons, including peptidergic nociceptors. miR-486 -/- mice exhibited normal baseline and neuropathic pain-like behaviors and recovered similarly to wild-type (WT) littermate controls in response to sciatic crush injury. On the other hand, DRG neurons derived from mice with a conditional deletion of IL6ST/gp130 in Na v1.8-expressing primary afferent nociceptors (SNS-gp130 -/-) show strongly compromised neuro-regeneration, which was significantly rescued by overexpressing miR-486, indicative of a specific role of miR-486 in IL-6/gp130-dependent neuro-regenerative processes. Our findings highlight context-dependent differential expression and roles of miRNAs after nerve injury driving nerve regeneration versus neuropathic pain.

MeSH

Peripheral Nerve Injuries, Neurons, Pain, Micrornas, Interleukin-6, Transducers, Nociceptors, Neuralgia, Sensory Receptor Cells