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

Abstract

Background: 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.

Exploring the therapeutic potential of Sirt6-enriched adipose stem cell-derived exosomes in myocardial ischemia–reperfusion injury: unfolding new epigenetic frontiers

“…Based on the ability to cross the vessel barrier, excellent biocompatibility, and low immunogenicity, exosomes have emerged as efficient nanoscale messengers for cells or cell-tissue communications [ 16 , 29 ]. Mounting evidence suggests that exosomes possess great capacity to deliver protective non-coding RNAs [ 30 , 31 ], miRNAs [ 32 , 33 ], and healthy organelles [ 34 ] for the treatment of ischemic diseases. ASCs are abundant in source, easy to be harvested and modified, and can robustly release exosomes, which would meet huge clinical demands in future [ 18 , 35 ].…”

Bone Marrow Mesenchymal Stromal Cell-Derived Exosomal Nrf2 Ameliorates Cerebral Ischemia-Reperfusion Injury by Transcriptionally Activating Lin28a

“…Bone marrow mesenchymal stromal cell-derived exosomes have protective effects against CIRI (13). Moreover, some molecules from BMSC-derived exosomes such as miR-133a-3p (32), long noncoding RNA KLF transcription factor 3 antisense RNA 1 (lncRNA KLF3-AS1) (33), and KLF transcription factor 4 (KLF4) (34) also improved CIRI. Our data showed that BMSC-derived exosomal NRF2 promoted the mRNA and protein expression of Lin28a.…”

Insight into extracellular vesicles in vascular diseases: intercellular communication role and clinical application potential

“…Additionally, elucidating the roles of all cargoes in EVs is challenging, and most researchers only pay close attention to the cargoes of interest, ignoring other potentially valuable content. Differential miRNA expression in tissues, cells, serum, plasma, and other samples has been detected by miRNA sequencing or microarray chip technology, and a single miRNA has been selected for subsequent research [ 201 – 204 ]. However, the mechanisms of other miRNAs and the synergistic mechanisms of multiple miRNAs have not been revealed.…”