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

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

doi:10.3724/abbs.2023275

Acta Biochimica et Biophysica Sinica (Jan 2024)

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

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

Affiliations

Cheng Haiqin: ["Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan 030001, China","Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China","Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Ministry of Education, Taiyuan 030001, China","Department of Medical, Fenyang Hospital of Shanxi Province, Lvliang 032200, China"]
Shi Yaqian: ["Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan 030001, China","Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China","Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Ministry of Education, Taiyuan 030001, China"]
Li Xuewei: ["Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan 030001, China","Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China","Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Ministry of Education, Taiyuan 030001, China"]
Jin Ning: ["Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan 030001, China","Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China","Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Ministry of Education, Taiyuan 030001, China"]
Zhang Mengyao: ["Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan 030001, China","Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China","Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Ministry of Education, Taiyuan 030001, China"]
Liu Zhizhen: ["Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan 030001, China","Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China","Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Ministry of Education, Taiyuan 030001, China"]
Liang Yuxiang: ["Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan 030001, China","Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Ministry of Education, Taiyuan 030001, China","Experimental Animal Center of Shanxi Medical University, Shanxi Key Laboratory of Human Disease and Animal Models, Taiyuan 030001, China"]
Xie Jun: ["Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan 030001, China","Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China","Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Ministry of Education, Taiyuan 030001, China"]

DOI: https://doi.org/10.3724/abbs.2023275
Journal volume & issue: Vol. 56
pp. 280 – 290

Abstract

Read online

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 intravenously 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.

Published in Acta Biochimica et Biophysica Sinica

ISSN: 1672-9145 (Print); 1745-7270 (Online)
Publisher: China Science Publishing & Media Ltd.
Country of publisher: China
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry; Science: Biology (General): Genetics
Website: https://www.sciengine.com/ABBS/home

About the journal

Abstract

Keywords