Dataset Information

Exosomes containing miR-451a is involved in the protective effect of cerebral ischemic preconditioning against cerebral ischemia and reperfusion injury.

ABSTRACT:

Aim

To study the role of exosomes in the protective effect of cerebral ischemic preconditioning (cerebral-IPC) against cerebral I/R injury.

Method

Mouse models of cerebral-IPC and MCAO/R were established as described previously, and their behavioral, pathological, and proteomic changes were analyzed. Neuro-2a subjected to OGD/R were treated with exosomes isolated from the plasma of sham-operated and cerebral-IPC mice. The differentially expressed miRNAs between exosomes derived from sham-operated (S-exosomes) and preconditioned (IPC-exosomes) mice were identified through miRNA array, and their targets were identified through database search. The control and OGD/R cells were treated with the IPC-exosomes, miRNA mimic or target protein inhibitor, and their viability, oxidative, stress and apoptosis rates were measured. The activated pathways were identified by analyzing the levels of relevant proteins.

Results

Cerebral-IPC mitigated the cerebral injury following ischemia and reperfusion, and increased the number of plasma exosomes. IPC-exosomes increased the survival of Neuro-2a cells after OGD/R. The miR-451a targeting Rac1 was upregulated in the IPC-exosomes relative to S-exosomes. The miR-451a mimic and the Rac1 inhibitor NSC23766 reversed OGD/R-mediated activation of Rac1 and its downstream pathways.

Conclusion

Cerebral-IPC ameliorated cerebral I/R injury by inducing the release of exosomes containing miR-451a.

SUBMITTER: Li H

PROVIDER: S-EPMC8025619 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The kidneys are prone to developing ischemia reperfusion injury (IRI) following certain renal surgeries and cardiovascular surgeries requiring cardiac arrest. Sevoflurane and ischemic preconditioning reportedly alleviate IRI, which is mediated via microRNAs. The present study compared anesthetic preconditioning (APC) and ischemic preconditioning (IPC) on microRNAs, which promote cell‑survival pathways in rats in a randomized controlled study. After undergoing right nephrectomy under general anesthesia, male Wistar rats (336±24 g) and were divided into four groups (IRI, APC, IPC and sham; n=7 each). The IRI group underwent 45 min clamping of the left renal vasculature, followed by 4 h of reperfusion. APC involved exposure to one minimum alveolar concentration sevoflurane for 15 min. IPC included three cycles of two‑min clamping and five‑min reperfusion. Blood and renal biopsy samples were assessed postoperatively to measure serum creatinine and to analyze renal microRNA (miR) expression using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) testing and their target pathways with Ingenuity Pathway Analysis™. The present study found that serum creatinine values in APC (0.71±0.08 mg/dl) and IPC (0.73±0.1 mg/dl) groups were lower than in the IRI group (0.96±0.13 mg/dl; P<0.05), indicating amelioration of IRI by APC and IPC. RT‑qPCR followed by pathway analysis indicated that APC and IPC affect 'protein kinase B (Akt)'. APC promoted miR‑17‑3p and suppressed miR‑27a. IPC promoted miR‑19a. All the miRs were predicted to regulate phosphorylated Akt, which promotes cell‑protection. Western blot analysis showed that expression of phosphorylated Akt increased and phosphatase and tensin homologue deleted from chromosome 10 (PTEN) decreased following APC and IPC. The present study concluded that APC and IPC affect different miRs, although they are estimated to similarly promote the PTEN/phosphoinositide 3‑kinase/Akt signaling pathway, resulting in reno‑protection.