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BMSC-derived exosomal miR-148b-3p attenuates OGD/R-induced HMC3 cell activation by targeting DLL4 and Notch1

Fang Yi1, Hui Xiao2, Mingyu Song3

  • 1Department of Geriatric Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.

Neuroscience Research
|September 23, 2023
PubMed

Insights

Bone mesenchymal stem cell-derived exosomes (BMSC-Exo) carrying miR-148b-3p can treat ischemic injury by inhibiting microglial activation via the DLL4/Notch1 pathway.

Area of Science:

  • Biomedical Science
  • Cell Biology
  • Neuroscience

Background:

  • Ischemic cerebrovascular disease (IC) involves microglial activation, contributing to neuronal damage.
  • Bone mesenchymal stem cell (BMSC)-derived exosomes (BMSC-Exo) show potential therapeutic effects for ischemic injuries.
  • Understanding the regulatory mechanisms of BMSC-Exo in microglial activation is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of BMSC-Exo miR-148b-3p in regulating oxygen-glucose deprivation/reoxygenation (OGD/R)-induced microglial activation.
  • To elucidate the underlying molecular mechanisms involving Delta-like ligand 4 (DLL4) and neurogenic locus notch homolog protein 1 (Notch1).

Main Methods:

  • Characterization of BMSC-Exo using Transmission Electron Microscopy (TEM) and qNano.
  • Assessment of HMC3 cell activation via MTT, flow cytometry, scratch, transwell, and ELISA assays.
  • Dual-luciferase reporter assay to confirm the targeting relationship between miR-148b-3p and DLL4/Notch1.

Main Results:

  • OGD/R reduced miR-148b-3p expression in HMC3 cells; BMSC-Exo treatment upregulated miR-148b-3p.
  • BMSC-Exo inhibited OGD/R-induced HMC3 cell viability, migration, and pro-inflammatory cytokine release, while promoting G0/G1 phase arrest.
  • miR-148b-3p directly targets DLL4 and Notch1, and its knockdown or inhibition of DLL4/Notch1 attenuated OGD/R-induced microglial activation.

Conclusions:

  • BMSC-Exo miR-148b-3p effectively inhibits OGD/R-induced microglial activation by targeting DLL4 and Notch1.
  • This pathway presents a novel therapeutic strategy for treating cerebral ischemia.
  • BMSC-Exo miR-148b-3p holds significant promise as a treatment for ischemic cerebrovascular disease.
Keywords:
Bone marrow mesenchymal stem cellExosomeIschemic strokeMiR-148b-3pMicroglia cell

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