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已发表论文
MFG-E8 在川崎病中的作用：内皮损伤及诊断潜力
Authors Pei Q, Zhang J, Li M, Yang P, Jing F, Yi Q
Received 17 June 2025
Accepted for publication 15 November 2025
Published 21 November 2025 Volume 2025:18 Pages 16365—16383
DOI https://doi.org/10.2147/JIR.S547634
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Tara Strutt
Qiongfei Pei,1– 3 Jing Zhang,1– 3 Mengling Li,1– 3 Penghui Yang,1– 3 Fengchuan Jing,1– 3 Qijian Yi1– 3
1Department of Cardiovascular Medicine, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, People’s Republic of China; 3National Clinical Key Cardiovascular Specialty, Key Laboratory of Children’s Important Organ Development and Diseases of Chongqing Municipal Health Commission, Chongqing, People’s Republic of China
Correspondence: Qijian Yi, Department of Cardiovascular Medicine, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China, Tel/Fax +86 02363624344, Email qjyi2003@hotmail.com
Background: Kawasaki disease (KD) is a systemic vasculitis predominantly affecting children under five years old, with coronary artery lesions (CALs) being a severe complication. Despite the effectiveness of intravenous immunoglobulin (IVIG) therapy, a subset of patients remains unresponsive, necessitating alternative strategies. Milk Fat Globule Epidermal Growth Factor 8 (MFG-E8) is a secreted glycoprotein that functions as a bridge between damaged cells and phagocytes, conferring the ability to regulate immunity and inflammation. This study aimed to investigate the potential role of MFG-E8 in KD pathogenesis.
Methods: Serum levels of MFG-E8 were measured via ELISA. CAWS was utilized to induce a murine model of coronary vasculitis, with MFG-E8 being administered intraperitoneally for treatment. Histological evaluation was conducted using H&E and IHC staining. Serum-stimulated THP-1 cells were co-cultured with endothelial cells to establish an inflammatory environment in vitro, with exogenous supplementation of MFG-E8. Pyroptosis-related markers were assessed by Western blot or immunofluorescence staining. Oxidative stress-related indicators were measured using commercially available assay kits.
Results: Serum MFG-E8 levels were significantly lower in KD patients, especially those with CALs, compared to febrile and healthy controls. ROC analysis showed that combining MFG-E8 with Fbg and TT improved the ability to distinguish KD from other febrile illnesses. Further analyses displayed negative correlations between MFG-E8 and parameters pointing to inflammation. In the murine model of vasculitis, MFG-E8 supplementation alleviated coronary artery inflammation, reduced endothelial cell pyroptosis, and mitigated oxidative stress. Similar results were presented in vitro experiments using KD serum-treated endothelial cells.
Conclusion: MFG-E8 represents a potential biomarker for the diagnosis of KD and exhibits protective effects against endothelial cell injury during the acute phase.
Keywords: Kawasaki disease, MFG-E8, endothelial cell pyroptosis, oxidative stress, coronary artery lesions
1Department of Cardiovascular Medicine, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, People’s Republic of China; 3National Clinical Key Cardiovascular Specialty, Key Laboratory of Children’s Important Organ Development and Diseases of Chongqing Municipal Health Commission, Chongqing, People’s Republic of China
Correspondence: Qijian Yi, Department of Cardiovascular Medicine, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China, Tel/Fax +86 02363624344, Email qjyi2003@hotmail.com
Background: Kawasaki disease (KD) is a systemic vasculitis predominantly affecting children under five years old, with coronary artery lesions (CALs) being a severe complication. Despite the effectiveness of intravenous immunoglobulin (IVIG) therapy, a subset of patients remains unresponsive, necessitating alternative strategies. Milk Fat Globule Epidermal Growth Factor 8 (MFG-E8) is a secreted glycoprotein that functions as a bridge between damaged cells and phagocytes, conferring the ability to regulate immunity and inflammation. This study aimed to investigate the potential role of MFG-E8 in KD pathogenesis.
Methods: Serum levels of MFG-E8 were measured via ELISA. CAWS was utilized to induce a murine model of coronary vasculitis, with MFG-E8 being administered intraperitoneally for treatment. Histological evaluation was conducted using H&E and IHC staining. Serum-stimulated THP-1 cells were co-cultured with endothelial cells to establish an inflammatory environment in vitro, with exogenous supplementation of MFG-E8. Pyroptosis-related markers were assessed by Western blot or immunofluorescence staining. Oxidative stress-related indicators were measured using commercially available assay kits.
Results: Serum MFG-E8 levels were significantly lower in KD patients, especially those with CALs, compared to febrile and healthy controls. ROC analysis showed that combining MFG-E8 with Fbg and TT improved the ability to distinguish KD from other febrile illnesses. Further analyses displayed negative correlations between MFG-E8 and parameters pointing to inflammation. In the murine model of vasculitis, MFG-E8 supplementation alleviated coronary artery inflammation, reduced endothelial cell pyroptosis, and mitigated oxidative stress. Similar results were presented in vitro experiments using KD serum-treated endothelial cells.
Conclusion: MFG-E8 represents a potential biomarker for the diagnosis of KD and exhibits protective effects against endothelial cell injury during the acute phase.
Keywords: Kawasaki disease, MFG-E8, endothelial cell pyroptosis, oxidative stress, coronary artery lesions