International Journal of Nanomedicine (Jan 2023)

Exosomal miR-133a-3p Derived from BMSCs Alleviates Cerebral Ischemia-Reperfusion Injury via Targeting DAPK2

  • Yang X,
  • Xu J,
  • Lan S,
  • Tong Z,
  • Chen K,
  • Liu Z,
  • Xu S

Journal volume & issue
Vol. Volume 18
pp. 65 – 78

Abstract

Read online

Xuanyong Yang,1,* Jiang Xu,1,* Shihai Lan,1 Zhigao Tong,1 Kang Chen,1 Zhizheng Liu,1 Shan Xu2 1Department of Neurosurgery, The First Affiliated Hospital, Nanchang University, Nanchang, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shan Xu, Department of Pathology, The First Affiliated Hospital of Nanchang University, No. 17 Yong Wai Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Email [email protected]: Cerebral ischemia-reperfusion (CI/R) injury is a subtype of complication after treatment of ischemic stroke. It has been reported that exosomes derived from BMSCs could play an important role in CI/R injury. However, whether BMSCs-derived exosomes could regulate CI/R injury via carrying miRNAs remains to be further explored.Methods: RNA sequencing was performed to identify the differentially expressed miRNAs. To mimic CI/R in vitro, SH-SY5Y cells were exposed to oxygen glucose deprivation/reoxygenation (OGD/R). The viability of SH-SY5Y cells was tested by CCK8 assay, and TUNEL staining was performed to detect the cell apoptosis.Results: MiR-133a-3p was identified to be reduced in exosomes derived from the plasma of patients with IS. Upregulation of miR-133a-3p significantly reversed OGD/R-induced SH-SY5Y cell growth inhibition. Consistently, BMSCs-derived exosomal miR-133a-3p could restore OGD/R-decreased SH-SY5Y cell proliferation via inhibiting apoptosis. Meanwhile, DAPK2 was a direct target of miR-133a-3p. In addition, OGD/R notably upregulated the level of DAPK2 and weakened the expressions of p-Akt and p-mTOR in SH-SY5Y cells, whereas exosomal miR-133a-3p derived from BMSCs notably reversed these phenomena. Exosomal miR-133a-3p derived from BMSCs could reverse OGD/R-induced cell apoptosis via inhibiting autophagy. Furthermore, exosomal miR-133a-3p derived from BMSCs markedly alleviated the symptom of CI/R injury in vivo.Conclusion: Exosomal miR-133a-3p derived from BMSCs alleviates CI/R injury via targeting DAPK2/Akt signaling. Thus, our study might shed new light on discovering new strategies against CI/R injury.Keywords: CI/R, BMSC, miR-133a-3p, DAPK2, autophagy

Keywords