Bioactive milk-derived nutrient MFG-E8 ameliorates skeletal muscle atrophy induced by mitochondria damage in aging rats via activating the MAPK/ERK signaling pathway

ABSTRACT: Sarcopenia is the age-related loss of muscle and fiber number and decreased regenerative capacity with increased abundance of reactive oxygen species levels and electron transport chain abnormalities. The aim of this study was to investigate the antisarcopenia effect of MFG-E8 in alleviati...

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Main Authors: Kaifang Guan, Xiaolin Liu, Weihong Lu, Yuhao Mao, Yirong Mao, Ying Ma, Rongchu Wang, Qiming Li
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Journal of Dairy Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S0022030224012414
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author Kaifang Guan
Xiaolin Liu
Weihong Lu
Yuhao Mao
Yirong Mao
Ying Ma
Rongchu Wang
Qiming Li
author_facet Kaifang Guan
Xiaolin Liu
Weihong Lu
Yuhao Mao
Yirong Mao
Ying Ma
Rongchu Wang
Qiming Li
author_sort Kaifang Guan
collection DOAJ
description ABSTRACT: Sarcopenia is the age-related loss of muscle and fiber number and decreased regenerative capacity with increased abundance of reactive oxygen species levels and electron transport chain abnormalities. The aim of this study was to investigate the antisarcopenia effect of MFG-E8 in alleviating skeletal muscle dysfunction induced by D-galactose, and reveal the mechanism promoting myoblast cell proliferation and mediating the cell cycle. This in vivo experiment showed that MFG-E8 can improve the antioxidant status and increase soleus muscle mass (35.61%) and fiber diameter (39.72%) in the aging rats. The western blot assay preliminarily proved that increased ERK phosphorylation determines the repairment of injured skeletal muscle, but not JNK and p38. In vitro experiments further verified that MFG-E8 can increase the number of mitochondria, cell vitality, cell density, and reduce apoptosis rate. Flow cytometry and quantitative real-time PCR proved that MFG-E8 promoted cell proliferation by upregulating mRNA expression of cyclin D1, cyclin E1, CDK, and downregulating mRNA expression of p21 and p27, thereby increasing the S and G2/M phase and decreasing the G0/G1 phase. Molecular level further proved that MFG-E8 mediated cell cycle and promoted cell proliferation by activating the MAPK/ERK signaling pathway.
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id doaj-art-823bd820fcbe41c3b2f71043f4cfd4fa
institution Kabale University
issn 0022-0302
language English
publishDate 2025-02-01
publisher Elsevier
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series Journal of Dairy Science
spelling doaj-art-823bd820fcbe41c3b2f71043f4cfd4fa2025-01-23T05:25:09ZengElsevierJournal of Dairy Science0022-03022025-02-01108211821197Bioactive milk-derived nutrient MFG-E8 ameliorates skeletal muscle atrophy induced by mitochondria damage in aging rats via activating the MAPK/ERK signaling pathwayKaifang Guan0Xiaolin Liu1Weihong Lu2Yuhao Mao3Yirong Mao4Ying Ma5Rongchu Wang6Qiming Li7School of Medicine and Health, Harbin Institute of Technology, Harbin 150001, Heilongjiang, ChinaSchool of Medicine and Health, Harbin Institute of Technology, Harbin 150001, Heilongjiang, ChinaSchool of Medicine and Health, Harbin Institute of Technology, Harbin 150001, Heilongjiang, ChinaCollege of Architectural Science and Engineering, Yangzhou University, Jiangsu 225000, ChinaSchool of Science, Shanghai Maritime University, Shanghai 200135, ChinaSchool of Medicine and Health, Harbin Institute of Technology, Harbin 150001, Heilongjiang, ChinaSchool of Medicine and Health, Harbin Institute of Technology, Harbin 150001, Heilongjiang, China; Corresponding authorsDairy Nutrition and Function, Key Laboratory of Sichuan Province, New Hope Dairy Co. Ltd., Chengdu, Sichuan 610023, China; Chengdu Molecular Power Biotechnology Co. Ltd., Chengdu, Sichuan 611732, China; Corresponding authorsABSTRACT: Sarcopenia is the age-related loss of muscle and fiber number and decreased regenerative capacity with increased abundance of reactive oxygen species levels and electron transport chain abnormalities. The aim of this study was to investigate the antisarcopenia effect of MFG-E8 in alleviating skeletal muscle dysfunction induced by D-galactose, and reveal the mechanism promoting myoblast cell proliferation and mediating the cell cycle. This in vivo experiment showed that MFG-E8 can improve the antioxidant status and increase soleus muscle mass (35.61%) and fiber diameter (39.72%) in the aging rats. The western blot assay preliminarily proved that increased ERK phosphorylation determines the repairment of injured skeletal muscle, but not JNK and p38. In vitro experiments further verified that MFG-E8 can increase the number of mitochondria, cell vitality, cell density, and reduce apoptosis rate. Flow cytometry and quantitative real-time PCR proved that MFG-E8 promoted cell proliferation by upregulating mRNA expression of cyclin D1, cyclin E1, CDK, and downregulating mRNA expression of p21 and p27, thereby increasing the S and G2/M phase and decreasing the G0/G1 phase. Molecular level further proved that MFG-E8 mediated cell cycle and promoted cell proliferation by activating the MAPK/ERK signaling pathway.http://www.sciencedirect.com/science/article/pii/S0022030224012414MFG-E8skeletal muscle atrophymitochondriaERK signaling pathwaycell cycle
spellingShingle Kaifang Guan
Xiaolin Liu
Weihong Lu
Yuhao Mao
Yirong Mao
Ying Ma
Rongchu Wang
Qiming Li
Bioactive milk-derived nutrient MFG-E8 ameliorates skeletal muscle atrophy induced by mitochondria damage in aging rats via activating the MAPK/ERK signaling pathway
Journal of Dairy Science
MFG-E8
skeletal muscle atrophy
mitochondria
ERK signaling pathway
cell cycle
title Bioactive milk-derived nutrient MFG-E8 ameliorates skeletal muscle atrophy induced by mitochondria damage in aging rats via activating the MAPK/ERK signaling pathway
title_full Bioactive milk-derived nutrient MFG-E8 ameliorates skeletal muscle atrophy induced by mitochondria damage in aging rats via activating the MAPK/ERK signaling pathway
title_fullStr Bioactive milk-derived nutrient MFG-E8 ameliorates skeletal muscle atrophy induced by mitochondria damage in aging rats via activating the MAPK/ERK signaling pathway
title_full_unstemmed Bioactive milk-derived nutrient MFG-E8 ameliorates skeletal muscle atrophy induced by mitochondria damage in aging rats via activating the MAPK/ERK signaling pathway
title_short Bioactive milk-derived nutrient MFG-E8 ameliorates skeletal muscle atrophy induced by mitochondria damage in aging rats via activating the MAPK/ERK signaling pathway
title_sort bioactive milk derived nutrient mfg e8 ameliorates skeletal muscle atrophy induced by mitochondria damage in aging rats via activating the mapk erk signaling pathway
topic MFG-E8
skeletal muscle atrophy
mitochondria
ERK signaling pathway
cell cycle
url http://www.sciencedirect.com/science/article/pii/S0022030224012414
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