Mesenchymal stem cell conditioned medium attenuates oxidative stress injury in hepatocytes partly by regulating the miR-486-5p/PIM1 axis and the TGF-β/Smad pathway

This study investigated the role of microRNA (miRNA) miR-486-5p in oxidative stress injury in hepatocytes under the treatment of mesenchymal stem cell conditioned medium (MSC-CM). The oxidative stress injury in hepatocytes (L02) was induced by H(2)O(2). Human umbilical cord blood MSC-CM (UCB-MSC-CM) was prepared. The effects of UCB-MSC-CM on the proliferation, apoptosis, and inflammatory response in L02 cells were detected by Cell Counting Kit-8 (CCK-8) assay, flow cytometry analysis, and enzyme-linked immunosorbent assay (ELISA). Subsequently, the target of miR-486-5p was predicted using bioinformatics analysis, and the possible signaling pathway addressed by miR-486-5p was explored using western blot. We found that miR-486-5p expression was elevated following oxidative stress injury and was reduced after UCB-MSC-CM treatment. UCB-MSC-CM protected L02 cells against H(2)O(2)-induced injury by downregulation of miR-486-5p. Proviral integration site for Moloney murine leukemia virus 1 (PIM1) was verified to be targeted by miR-486-5p. UCB-MSC-CM upregulated the expression of PIM1 reduced by H(2)O(2) in L02 cells. Additionally, silencing PIM1 attenuated the protective effects of miR-486-5p downregulation against oxidative stress injury. We further demonstrated that UCB-MSC-CM inhibited the TGF-β/Smad signaling in H(2)O(2-)treated L02 cells by the miR-486-5p/PIM1 axis. Overall, UCB-MSC-CM attenuates oxidative stress injury in hepatocytes by downregulating miR-486-5p and upregulating PIM1, which may be related to the inhibition of TGF-β/Smad pathway.