Exosomes Derived from BMSCs Ameliorate Intestinal Ischemia-Reperfusion Injury by Regulating miR-144-3p-Mediated Oxidative Stress.

BACKGROUND

Intestinal ischemia-reperfusion (I/R) injury is a critical pathophysiological process involved in many acute and critical diseases, and it may seriously threaten the lives of patients. Exosomes derived from bone marrow mesenchymal stem cells (BMSC-exos) may be an effective therapeutic approach for I/R injury.

AIMS

This study aimed to investigate the role and possible mechanism of BMSC-exos in intestinal I/R injury in vivo and in vitro based on the miR-144-3p and PTEN/Akt/Nrf2 pathways.

METHODS

BMSC-exos were isolated from mouse BMSCs by super centrifugation methods. The effects of BMSC-exos on I/R intestinal injury, intestinal cell apoptosis, oxidative stress and the PTEN/Akt/Nrf2 pathway were explored in vivo and in vitro. Furthermore, the relationship between miR-144-3p and PTEN was confirmed by a dual-luciferase reporter assay. The miR-144-3p mimic and inhibitor were used to further clarify the role of miR-144-3p in the mitigation of intestinal I/R by BMSC-exos.

RESULTS

BMSC-exos effectively alleviated intestinal pathological injury, reduced intestinal cell apoptosis, relieved oxidative stress and regulated the PTEN/Akt/Nrf2 pathway in vivo and in vitro. In addition, miR-144-3p was significantly reduced in the oxygen and glucose deprivation/reperfusion cell model, and miR-144-3p could directly target PTEN to regulate its expression. Additional studies showed that changing the expression of miR-144-3p in BMSC-exos significantly affected the regulation of intestinal injury, intestinal cell apoptosis, oxidative stress and the PTEN/Akt/Nrf2 pathway in I/R, suggesting that miR-144-3p in BMSC-exos plays an important role in regulating the PTEN/Akt/Nrf2 during intestinal I/R.

CONCLUSIONS

BMSC-exos carrying miR-144-3p alleviated intestinal I/R injury by regulating oxidative stress.