1. Academic Validation
  2. miR-150-3p enhances neuroprotective effects of neural stem cell exosomes after hypoxic-ischemic brain injury by targeting CASP2

miR-150-3p enhances neuroprotective effects of neural stem cell exosomes after hypoxic-ischemic brain injury by targeting CASP2

  • Neurosci Lett. 2022 May 14;779:136635. doi: 10.1016/j.neulet.2022.136635.
Hongcheng Luo 1 Guangbin Ye 2 Yu Liu 2 Deyou Huang 3 Qisheng Luo 4 Wencheng Chen 5 Zhongquan Qi 6
Affiliations

Affiliations

  • 1 Department of Biology, Medical College of Guangxi University, Nanning 53004, China; Department of Medical Laboratory, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000 Guangxi, China.
  • 2 Department of Biology, Medical College of Guangxi University, Nanning 53004, China.
  • 3 Department of Radiology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000 Guangxi, China.
  • 4 Department of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000 Guangxi, China.
  • 5 Department of Medical Laboratory, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000 Guangxi, China.
  • 6 Department of Biology, Medical College of Guangxi University, Nanning 53004, China. Electronic address: [email protected].
Abstract

Brains are vulnerable to ischemic/hypoxic damage, which are directly caused by stroke, hypoxic-ischemic encephalopathy and other cerebral diseases. Currently, therapeutic strategies against cerebral ischemia and hypoxia are extremely limited. Recent studies have indicated that stem cell-derived exosomes play a neuroprotective role in hypoxic-ischemic brain injury. However, the treatment mechanism remains unclear. In this study, we cultured neural stem cells (NSCs) in vitro successfully. Exosomes isolated from NSCs (NSCs-Ex) inhibited the Apoptosis while promoting the proliferation of SH-SY5Y cells both in normal and oxygen-glucose deprivation (OGD) culture conditions. Moreover, in vivo studies demonstrated that NSCs-Ex significantly reduced the infarction area in the middle cerebral artery occlusion (MCAO) model and suppressed the Apoptosis of neurons. Furthermore, miR-150-3p was identified as the most abundantly expressed miRNA in exosomes compared to their parent NSCs. The miR-150-3p mimic displayed neuroprotective effects while miR-150-3p inhibitor exacerbated nerve injury both in vivo and in vitro. We further identified CASP2 as a miR-150-3p target. Thus, our data indicate that NSC-Ex facilitate the neuroprotective effects via transfer of miR-150-3p which targets CASP2, thus suppressing neuronal Apoptosis after brain injury. Our results suggest that NSCs-Ex prevent cerebral injury by transferring miR-150-3p which promotes neurons proliferation by inhibiting CASP2 signaling pathway.

Keywords

Apoptosis and proliferation; Exosomes; Hypoxic-ischemic brain injury; Neural stem cells; miRNAs.

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