ADSCs‐exo attenuates hepatic ischemia–reperfusion injury after hepatectomy by inhibiting endoplasmic reticulum stress and inflammation

Abstract

Hepatic ischemia-reperfusion (I/R) injury commonly occurs during liver surgery.Exosomes from adipose-derived stem cells (ADSCs-exo) induce a hepatoprotective effect during hepatic I/R injury. This study aimed to investigate the possible mechanism by which ADSCs-exo attenuates hepatic I/R injury in rats. Rats were randomly divided into four groups: Sham, I30R + PH, ADSCs, and ADSCs-exo groups. Liver tissues were collected immediately after 24 h of reperfusion for further analyses. The content of inflammatory factors in liver tissue was detected using enzyme-linked immunosorbent assay. The pathological changes in liver tissue were analyzed using HE staining. Transmission electron microscopy was used to visualize the ultrastructural changes of hepatocytes. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to detect the expression of endoplasmic reticulum stress (ERS)-related genes and proteins. Liver histomorphology and hepatocyte ultrastructure changes improved after ADSCs-exo treatment.Moreover, ADSCs-exo treatment significantly downregulated tumor necrosis factorα, interleukin-1β (IL-1β), and IL-6 levels while upregulating IL-10 levels. Western blot analysis suggested that the protein expressions of GRP78, p-PERK, p-eIF2α, p-IRE1α, XBP1s, ATF-6, ATF-4, CHOP, p-JNK, cleaved-Caspase-3, cleaved Caspase-9, and cleaved Caspase-12 significantly decreased after ADSCs-exo treatment. RT-qPCR results demonstrated that mRNA expression of GRP78, IRE1α, XBP1, ATF-6, ATF-4, CHOP, JNK, Caspase-3, Caspase-9, and Caspase-12 markedly reduced after ADSCs-exo treatment. In conclusion, ADSCs-exo protects against hepatic I/R injury after hepatectomy by inhibiting ERS and inflammation. Therefore, ADSCs-exo can be considered as a viable option for the treatment of hepatic I/R injury.

Vitamin D receptor mediates liver ischemia and reperfusion injury by autophagy-regulated M2 macrophage polarization

“…Meanwhile, VDR deficiency can deteriorate liver IR injury by disturbing M2 macrophage polarization. Previous research proved that VDR regulates inflammation through autophagy ( Lu et al, 2020 ; Fang et al, 2021 ) and M1/2 macrophage polarization ( Wang et al, 2017 ). We also found that the autophagy agonist RAP or inhibitor CQ could respectively enhance or weaken the role of VDR on M2 macrophage polarization in Figure 4 .…”

Adipose stem cells in tissue regeneration and repair: From bench to bedside

“…Furthermore, ADSCs can secrete a large number of cytokines to exert their effects. ADSCs can secrete cytokines such as IL-1α, IL-6, and IL-10 to play an anti-inflammatory role [ 13 ]. IL-1α binds to IL-1typeⅠreceptor and induces structural changes of IL-1R, interacts with IL-1RAcP, and initiates NF-κB signal transduction cascade [ 14 ].…”

Exosomes: Potential Next-Generation Nanocarriers for the Therapy of Inflammatory Diseases

“…The EXs’ treatment significantly downregulated IL-6, interleukin-1β (IL-1β), and TNF-α levels and upregulated IL-10 levels. EXs displayed their hepatoprotective properties by preventing endoplasmic reticulum stress and inflammation [ 107 ].…”