Exosomes Derived from miR-183-Overexpressing Human Adipose-Derived Stem Cells Alleviate Hepatic Ischemia-Reperfusion (I/R) Injury through miR-183/ALOX5 axisExosomes Derived from miR-183-Overexpressing Human Adipose-Derived Stem Cells Alleviate Hepatic Ischemia-Reperfusion (I/R) Injury through miR-183/ALOX5 Axis

Abstract

BackgroundIschemia-reperfusion (I/R) injury a crucial factor causing liver injury in clinic. Recent research confirmed that human adipose-derived stem cells (ADSCs) can differentiate into functional hepatocytes. However, the mechanism of ADSCs in the treatment of liver injury remains unclear.MethodsCharacteristics of ADSCs were first identified, and exosomes from miR-183-overexpressed ADSCs were isolated and identified. And the function and mechanism of microRNA-183 (miR-183) and arachidonate 5-lipoxygenase (ALOX5) were monitored through biological experiments in HL-7702 cells with I/R injury or I/R rats. ResultsWe proved that inhibition of exosomes from the identified ADSCs prevented proliferation, induced apoptosis and downregulated miR-183 in HL-7702 cells with I/R injury, while exosomes derived from ADSCs played an opposite role on the proliferation and apoptosis of HL-7702 cells with I/R injury in comparison with exosome inhibitors by upregulating miR-183. Meanwhile, the effect of miR-183 alone was similar to that of exosomes derived from ADSCs. Besides, ALOX5, as a target gene of miR-183, was involved in the related functions of miR-183. Moreover, in vivo experiments further confirmed miR-183 or exosomes from ADSCs also could improve liver injury of rats and downregulate MAPK and NF-κB pathways.ConclusionAll these findings testified that exosomes derived from miR-183-overexpressing ADSCs have a significant protective effect on hepatic I/R injury by regulating miR-183/ALOX5 axis, which might provide therapeutic strategy for liver injury.