Bone marrow mesenchymal stem cells-derived exosomes promote spinal cord injury repair through the miR-497-5p/TXNIP/NLRP3 axis

J Mol Histol. 2024 Nov 29;56(1):16. doi: 10.1007/s10735-024-10289-z.

Abstract

Bone marrow mesenchymal stem cells (BMSCs) indicate a repairing prospect to treat spinal cord injury, a major traumatic disease. This study investigated the repair effect of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) on spinal cord injury. BMSCs were collected to extract BMSC-Exos which were identified by different means. The SCI model of rats was established, the motor behavior was scored by BBB field test, and the spinal cord tissues were separated and stained by HE, Nissl, and Tunel, respectively, as well as analyzed to measure inflammatory and oxidative stress responses. PC12 cells were co-cultured with Exos and analyzed by CCK-8 and flow cytometry to measure cell proliferation and apoptosis. BMSC-Exos improved SCI in rats with the recovery of motor function, alleviation of pathological conditions, and reduction of apoptosis, inflammatory responses, and oxidative stress. BMSC-Exos increased miR-497-5p expression, and miR-497-5p overexpression strengthened the protective effect of BMSC-Exos on SCI. miR-497-5p targeted inactivation of TXNIP/NLRP3 pathway. TXNIP saved the repair effect of miR-497-5p-carrying BMSC-Exos on SCI rats. miR-497-5p-carrying BMSC-Exos alleviated apoptosis and induced proliferation of H2O2-treated PC12 cells. BMSC-Exos promote SCI repair via the miR-497-5p/TXNIP/NLRP3 axis, which may be a target for alleviating SCI-associated nerve damage.

Keywords: Exosomes; NLRP3; Spinal cord injury; miR-497-5p.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation
  • Disease Models, Animal
  • Exosomes* / metabolism
  • Male
  • Mesenchymal Stem Cells* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein* / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Oxidative Stress
  • PC12 Cells
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Spinal Cord Injuries* / genetics
  • Spinal Cord Injuries* / metabolism
  • Spinal Cord Injuries* / pathology
  • Spinal Cord Injuries* / therapy

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • MicroRNAs
  • Nlrp3 protein, rat
  • TXNIP protein, rat
  • Carrier Proteins
  • Cell Cycle Proteins