Attenuation of hepatic ischemia‑reperfusion injury by adipose stem cell‑derived exosome treatment via ERK1/2 and GSK‑3β signaling pathways.

Exosomes are an emerging therapeutic tool for the treatment of tissue injuries. In the present study, the protective effect of isolated exosomes from adipose‑derived stem cells (ADSCs‑exo) against hepatic ischemia‑reperfusion (I/R) injury was explored. Hepatic I/R injury was achieved by inducing ischemia for 60 min followed by reperfusion for 2 and 6 h. Pre‑treatment with ADSCs‑exo revealed a significant reduction in necrosis and apoptosis in liver tissue induced by I/R injury. Hypoxic oxidative stress was managed by exosome‑mediated reduced reactive oxygen species and increased superoxide dismutase that in turn protected mitochondrial damage and apoptosis. Reduction in inflammatory mediators such as IL‑1β and TNF‑α was also observed and protection of hepatocytes from I/R injury was evidenced by a significant decrease in biochemical markers of liver damage (alanine transaminase, aspartate transaminase and lactate dehydrogenase). Exosomal prostaglandin E2 (PGE2)‑mediated ERK1/2 and GSK‑3β phosphorylation were revealed to increase Bcl‑2 and decrease Bax expression with mitochondrial permeability transition pore‑inhibition which may be considered a prime mechanism of exosome‑mediated hepatoprotection. In conclusion, our results indicated that ADSCs‑exo pre‑treatment is effective in protecting liver I/R injury.