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
  • [21] Mulberry Leaf and Neochlorogenic Acid Alleviates Glucolipotoxicity-Induced Oxidative Stress and Inhibits Proliferation/Migration via Downregulating Ras and FAK Signaling Pathway in Vascular Smooth Muscle Cell
    Yang, Tsung-Yuan
    Wu, Yi-Liang
    Yu, Meng-Hsun
    Hung, Tung-Wei
    Chan, Kuei-Chuan
    Wang, Chau-Jong
    NUTRIENTS, 2022, 14 (15)
  • [22] Amnion-Derived Mesenchymal Stem Cell Exosomes-Mediated Autophagy Promotes the Survival of Trophoblasts Under Hypoxia Through mTOR Pathway by the Downregulation of EZH2
    Chu, Yijing
    Chen, Weiping
    Peng, Wei
    Liu, Yong
    Xu, Lin
    Zuo, Jianxin
    Zhou, Jun
    Zhang, Yan
    Zhang, Ning
    Li, Jing
    Liu, Ling
    Yao, Ke
    Gao, Guoqiang
    Wang, Xiaofei
    Han, Rendong
    Liu, Chong
    Li, Yan
    Zhou, Huansheng
    Huang, Yuxiang
    Ye, Yuanhua
    FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2020, 8
  • [23] Mesenchymal Stem Cell-Derived Exosomes Ameliorate Diabetic Kidney Disease Through the NLRP3 Signaling Pathway
    Wang, Yinghui
    Liu, Jiaxi
    Wang, Honggang
    Lv, Shasha
    Liu, Qingzhen
    Li, Shan
    Yang, Xue
    Liu, Gang
    STEM CELLS, 2023, 41 (04) : 368 - 383
  • [24] Mesenchymal stem cell-derived exosomes ameliorate diabetic kidney disease through NOD2 signaling pathway
    Wang, Yinghui
    Lu, Donglin
    Lv, Shasha
    Liu, Xiangchun
    Liu, Gang
    RENAL FAILURE, 2024, 46 (02)
  • [25] Human mesenchymal stem cells-derived exosomes attenuate liver ischemia/reperfusion injury by up regulation of notch-1-related autophagy in CD4 T cell
    Zhang, Xiaomei
    Zheng, Jun
    Cai, Jianye
    Chen, Liang
    Liu, Wei
    Yang, Yang
    JOURNAL OF HEPATOLOGY, 2019, 70 (01) : E803 - E803
  • [26] Mitofusin2 Induces Cell Autophagy of Pancreatic Cancer through Inhibiting the PI3K/Akt/mTOR Signaling Pathway
    Xue, Ran
    Meng, Qinghua
    Lu, Di
    Liu, Xinjuan
    Wang, Yanbin
    Ha, Jianyu
    OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2018, 2018
  • [27] Effects of Gastric Cancer Cell-Derived Exosomes on the Immune Regulation of Mesenchymal Stem Cells by the NF-kB Signaling Pathway
    Shen, Yamei
    Xue, Chunling
    Li, Xuechun
    Ba, Li
    Gu, Junjie
    Sun, Zhao
    Han, Qin
    Zhao, Robert Chunhua
    STEM CELLS AND DEVELOPMENT, 2019, 28 (07) : 464 - 476
  • [28] Mitofusin2 induces cell autophagy of pancreatic cancer through inhibiting the PI3K/Akt/mTOR signaling pathway
    Xue, Ran
    Hao, Jianyu
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2018, 33 : 533 - 533
  • [29] Bone marrow mesenchymal stem cell-derived exosomes attenuate D-GalN/LPS-induced hepatocyte apoptosis by activating autophagy in vitro
    Zhao, Shuxian
    Liu, Yan
    Pu, Zenghui
    DRUG DESIGN DEVELOPMENT AND THERAPY, 2019, 13 : 2887 - 2897
  • [30] Adipose Mesenchymal Stem Cell-Derived Exosomes Promote Wound Healing Through the WNT/β-catenin Signaling Pathway in Dermal Fibroblasts
    Cong Li
    Yu An
    Yu Sun
    Fan Yang
    Quanchen Xu
    Zhiguo Wang
    Stem Cell Reviews and Reports, 2022, 18 : 2059 - 2073