Role of ferroptosis in regulating liver fibrosis inhibition by bone marrow mesenchymal stem cells
Objective To investigate the role of ferroptosis in the regulation of hepatic stellate cells activation and liver fibrosis by bone marrow mesenchymal stem cells.Methods In total,5 male SD rats(provided by the Animal Experimental Center of Beijing Academy of Military Medical Sciences)were intra-peritoneally injected with olive oil for 12 weeks as the control group,and 15 SD rats were intraperitoneally injected with olive oil containing 40%CC14 for 8 weeks to establish rat liver fibrosis model,and were divid-ed into model group,BMMSCs treatment group and berberine group,5 per group.Rat hepatic stellate cells were divided into control group(Ctrl),platelet-derived growth factor BB(PDGF-BB)activation group,PDGF-BB+BMMSCs co-culture group,PDGF-BB+erastin group and PDGF-BB+BMMSCs+fer-1 group.Liver pathology was evaluated by hematoxylin and eosin(HE)and Sirius red staining,and the levels of ma-londialdehyde(MDA)and glutathione(GSH)were detected.Fibrosis and ferroptosis indicators were detec-ted by Western blotting and immunofluorescence.Data between two groups were compared by independent sample t test;data between three groups and above were analyzed by one-way analysis of variance.Results The degeneration,necrosis and collagen fiber deposition of hepatocytes in BMMSCs group were significantly reduced;the expression level of α-smooth muscle actin(α-SMA)in BMMSCs co-culture group was lower than PDGF-BB activation group(0.80±0.10 vs.1.13±0.06,F=32.914,P<0.05).The MDA con-tent in BMMSCs group was higher than model group[(0.37±0.02)vs.(0.23±0.02)μmoVmg,F=56.360,P<0.05].The MDA content of BMMSCs co-culture group was higher than PDGF-BB activation group[(1.54±0.18)vs.(1.14±0.06)nmol/mg prot,F=16.397,P<0.05],and the GSH content was lower than PDGF-BB activation group[(0.63±0.05)vs.(0.96±0.03)μg/106 cells,F=50.638,P<0.05].The cell viability of fer-1 pretreatment group was higher than BMMSCs co-culture group[(78.50±2.73)%vs.(24.07±8.92)%,F=89.533,P<0.05],and fer-1 inhibited BMMSCs-media-ted induction of ferroptosis and alleviated fibrosis.Conclusion Ferroptosis is involved in the process of BMMSCs inhibiting HSCs activation and alleviating liver fibrosis.
Bone marrow mesenchymal stem cellsLiver fibrosisFerroptosis