Human umbilical cord mesenchymal stem cells protect against ferroptosis in acute liver failure through the IGF1-hepcidin-FPN1 axis and inhibiting iron loading  

作　　者：Haiqin Cheng Yaqian Shi Xuewei Li Ning Jin Mengyao Zhang Zhizhen Liu Yuxiang Liang Jun Xie 

机构地区：[1]Shanxi Key Laboratory of Birth Defect and Cell Regeneration,Shanxi Medical University,Taiyuan 030001,China [2]Department of Biochemistry and Molecular Biology,Shanxi Medical University,Taiyuan 030001,China [3]Key Laboratory of Coal Environmental Pathogenicity and Prevention,Shanxi Medical University,Ministry of Education,Taiyuan 030001,China [4]Department of Medical,Fenyang Hospital of Shanxi Province,Lvliang 032200,China [5]Experimental Animal Center of Shanxi Medical University,Shanxi Key Laboratory of Human Disease and Animal Models,Taiyuan 030001,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第2期280-290,共11页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grant from the Natural Science Foundation of Shanxi Province(No.202103021223243).

摘　　要：Acute liver failure(ALF)is a significant global issue with elevated morbidity and mortality rates.There is an urgent and pressing need for secure and effective treatments.Ferroptosis,a novel iron-dependent regulation of cell death,plays a significant role in multiple pathological processes associated with liver diseases,including ALF.Several studies have demonstrated that mesenchymal stem cells(MsCs)have promising therapeutic potential in the treatment of ALF.This study aims to investigate the positive effects of MSCs against ferroptosis in an ALF model and explore the underlying molecular mechanisms of their therapeutic function.Our results show that in-travenously injected MsCs protect against ferroptosis in ALF mouse models.MsCs decrease iron deposition in the liver of ALF mice by downregulating hepcidin level and upregulating FPN1 level.MSCs labelled with Dil are mainly observed in the hepatic sinusoid and exhibit colocalization with the macrophage marker CD11b fluorescence.ELiSA demonstrates a high level of IGF1 in the CCL4+MSC group.Suppressing the IGF1 effect by the PPP blocks the therapeutic effect of MSCs against ferroptosis in ALF mice.Furthermore,disruption of IGF1 function results in iron deposition in the liver tissue due to impaired inhibitory effects of MsCs on hepcidin level.Our findings suggest that MSCs alleviate ferroptosis induced by disorders of iron metabolism in ALF mice by elevating IGF1 level.Moreover,MSCs are identified as a promising cell source for ferroptosis treatment in ALF mice.

关 键 词：mesenchymal stem cell acute liver failure ferroptosis iron loading insulin-like growth factor-1 

分 类 号：R575[医药卫生—消化系统] R329.2[医药卫生—内科学]