Muscle-derived Stem Cell Exosomes Enhance Autophagy through the Regulation of the mTOR Signaling Pathway to Attenuate Glucolipotoxicity-induced Pancreatic Β-cell Injury

被引:0
|
作者
Zeng, Xiang-Yu [1 ]
Liu, Zi-Wen [1 ]
Li, Hao-Ze [1 ]
Liu, Jian-Yu [1 ]
机构
[1] Harbin Med Univ, Dept Emergency Surg, Affiliated Hosp 2, Harbin 150001, Heilongjiang, Peoples R China
关键词
Muscle-derived stem cells; exosomes; mTOR signaling pathway; pancreatic beta-cells; autophagy; oxidative stress; THERAPY; REPAIR;
D O I
10.2174/011574888X288930240523045700
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Background Diabetes mellitus (DM) refers to a series of metabolic disorders, including elevated blood glucose level diseases due to insufficient insulin secretion or insulin resistance.Objective To investigate the effect and protective mechanism of muscle-derived stem cell exosomes (MDSC-Exo) on glucolipotoxicity-induced pancreatic beta cell injury.Methods Primary rat muscle-derived stem cells (MDSCs) were isolated and cultured. After the completion of the third-generation culture for MDSCs, MDSC-Exo was isolated. Then, the morphology and diameter of exosomes were observed by means of electron microscopy and nanoparticle tracking analysis (NTA) instrument. The expression of exosome-related proteins CD63, TSG101 and Calnexin was detected by western blot. After stimulation of rat insulinoma cell line INS-1 with high glucose/palmitic acid (HG/PA) and/or MDSC-Exo, cell viability and apoptosis were measured through MTT and flow cytometry (FCT), respectively. Biochemical reagents were utilized for the examination of the levels of superoxide dismutase (SOD) and malondialdehyde (MDA); enzyme-linked immunosorbent assay (ELISA) for the levels of cellular insulin secretion, and the western blot for the expression level of LC3, p62, AKT, p-AKT, mTOR and p-mTOR.Results MDSC-Exo was successfully isolated and identified, and it was found that MDSC-Exo could reduce HG/PA-induced apoptosis as well as MDA levels in INS-1 cells. Also, MDSC-Exo could significantly increase cell viability, insulin secretion ability within 24 hours and SOD level. Besides, MDSC-Exo was able to significantly increase the LC3-II/I ratio, decrease the expression level of p62, and promote autophagy in the cells. Aside from what has been mentioned, MDSC-Exo showed a significant reduction effect on p-Akt and p-mTOR level as well as p-Akt/Akt and p-mTOR/mTOR ratios.Conclusion MDSC-Exo can alleviate oxidative stress and enhance autophagy by inhibiting Akt/mTOR signaling pathway activation. Then, the inhibition of apoptosis and the promotion of insulin secretion can be achieved to alleviate glucolipotoxicity-induced pancreatic beta cell injury.
引用
收藏
页数:8
相关论文
共 50 条
  • [31] Adipose Mesenchymal Stem Cell-Derived Exosomes Promote Wound Healing Through the WNT/β-catenin Signaling Pathway in Dermal Fibroblasts
    Li, Cong
    An, Yu
    Sun, Yu
    Yang, Fan
    Xu, Quanchen
    Wang, Zhiguo
    STEM CELL REVIEWS AND REPORTS, 2022, 18 (06) : 2059 - 2073
  • [32] Stem cell-derived exosomes prevent pyroptosis and repair ischemic muscle injury through a novel exosome/circHIPK3/ FOXO3a pathway
    Yan, Bing
    Zhang, Yu
    Liang, Chun
    Liu, Bin
    Ding, Fengzhi
    Wang, Yanli
    Zhu, Bao
    Zhao, Ranzun
    Yu, Xi-Yong
    Li, Yangxin
    THERANOSTICS, 2020, 10 (15): : 6728 - 6742
  • [33] Adipose Mesenchymal Stem Cell-Derived Exosomes Enhance PC12 Cell Function through the Activation of the PI3K/AKT Pathway
    Xie, Yong
    Chen, Yangping
    Zhu, Yuyuan
    Chen, Xia
    Lin, Tiecheng
    Zhou, Dan
    STEM CELLS INTERNATIONAL, 2021, 2021
  • [34] miR-149 Alleviates Ox-LDL-Induced Endothelial Cell Injury by Promoting Autophagy through Akt/mTOR Pathway
    Zhu, Zhongsheng
    Li, Jinyu
    Tong, Rui
    Zhang, Xiaorong
    Yu, Bo
    CARDIOLOGY RESEARCH AND PRACTICE, 2021, 2021
  • [35] Endometrial stem cell-derived exosomes repair cisplatin-induced premature ovarian failure via Hippo signaling pathway
    Wang, Lijun
    Wang, Lihui
    Wang, Rongli
    Xu, Ting
    Wang, Jingyuan
    Cui, Zhiwei
    Cheng, Feiyan
    Wang, Wei
    Yang, Xinyuan
    HELIYON, 2024, 10 (10)
  • [36] Bone Marrow Mesenchymal Stem Cell-Derived Exosomal miRNA-29c Decreases Cardiac Ischemia/Reperfusion Injury Through Inhibition of Excessive Autophagy via the PTEN/Akt/mTOR Signaling Pathway
    Li, Te
    Gu, Junlian
    Yang, Ou
    Wang, Jianmeng
    Wang, Yonggang
    Kong, Jian
    CIRCULATION JOURNAL, 2020, 84 (08) : 1304 - +
  • [37] Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Ameliorate Aging-Induced BTB Impairment in Porcine Testes by Activating Autophagy and Inhibiting ROS/NLRP3 Inflammasomes via the AMPK/mTOR Signaling Pathway
    Zhou, Yi
    Yan, Jiale
    Qiao, Limin
    Zeng, Jiaqin
    Cao, Fuyu
    Sheng, Xihui
    Qi, Xiaolong
    Long, Cheng
    Liu, Bingying
    Wang, Xiangguo
    Yao, Hua
    Xiao, Longfei
    ANTIOXIDANTS, 2024, 13 (02)
  • [38] LncRNA Hoxb3os protects podocytes from high glucose-induced cell injury through autophagy dependent on the Akt-mTOR signaling pathway
    Jin, Juan
    Gong, Jianguang
    Zhao, Li
    Li, Yiwen
    He, Qiang
    ACTA BIOCHIMICA POLONICA, 2021, 68 (04) : 619 - 625
  • [39] SPARCL1 Influences Bovine Skeletal Muscle-Derived Satellite Cell Migration and Differentiation through an ITGB1-Mediated Signaling Pathway
    Wang, Yuxin
    Liu, Shuaiyu
    Yan, Yunqin
    Li, Shufeng
    Tong, Huili
    ANIMALS, 2020, 10 (08): : 1 - 14
  • [40] Mesenchymal Stem Cell-Derived Exosomes Attenuate Murine Cytomegalovirus-Infected Pneumonia via NF-κB/NLRP3 Signaling Pathway
    Chen, Fei
    Chen, Zhida
    Wu, Hui-Ting
    Chen, Xin-Xiang
    Zhan, Peiqi
    Wei, Zheng-Yi
    Ouyang, Zizhang
    Jiang, Xueyan
    Shen, Ao
    Luo, Min-Hua
    Liu, Qifa
    Zhou, Yue-Peng
    Qin, Aiping
    VIRUSES-BASEL, 2024, 16 (04):