Oxidative Stress-Mediated Thrombospondin-2 Upregulation Impairs Bone Marrow-Derived Angiogenic Cell Function in Diabetes Mellitus

被引:48
|
作者
Bae, Ok-Nam [4 ,5 ]
Wang, Jie-Mei [1 ,2 ,3 ]
Baek, Seung-Hoon [4 ,6 ]
Wang, Qingde [1 ,2 ,3 ]
Yuan, Hong [1 ]
Chen, Alex F. [1 ,2 ,3 ]
机构
[1] Cent S Univ, Xiangya Hosp 3, Ctr Clin Pharmacol, Dept Cardiol, Changsha 410013, Hunan, Peoples R China
[2] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA
[3] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA
[4] Michigan State Univ, Dept Pharmacol & Toxicol, E Lansing, MI 48824 USA
[5] Hanyang Univ, Coll Pharm, Ansan, South Korea
[6] Ajou Univ, Coll Pharm, Suwon 441749, Gyeonggido, South Korea
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
angiogenesis inhibitors; diabetes; oxidative stress; stem cells; thrombospondin-2; human; ENDOTHELIAL PROGENITOR CELLS; MICRORNA EXPRESSION; PROLIFERATION; DISEASE; PATHOPHYSIOLOGY; PHENOTYPE; PROTECTS;
D O I
10.1161/ATVBAHA.113.301609
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective Circulating angiogenic cells play an essential role in angiogenesis but are dysfunctional in diabetes mellitus characterized by excessive oxidative stress. We hypothesize that oxidative stress-mediated upregulation of thrombospondin-2 (TSP-2), a potent antiangiogenic protein, contributes to diabetic bone marrow-derived angiogenic cell (BMAC) dysfunction. Approach and Results BMACs were isolated from adult male type 2 diabetic db/db mice and control db/+ (C57BLKS/J) mice. In Matrigel tube formation assay, angiogenic function was impaired in diabetic BMACs, accompanied by increased oxidative stress and nicotinamide adenine dinucleotide phosphate oxidase activity. BMAC angiogenic function was restored by overexpression of dominant negative Rac1 or by overexpression of manganese superoxide dismutase. TSP-2 mRNA and protein were both significantly upregulated in diabetic BMACs, mediated by increased oxidative stress as shown by a decrease in TSP-2 level after overexpression of dominant negative Rac1 or manganese superoxide dismutase. Silencing TSP-2 by its small interfering RNA in diabetic BMACs improved BMAC function in tube formation, adhesion, and migration assays. Notably, the upregulation of TSP-2 was also found in BMACs from streptozotocin-induced type 1 diabetic mice, and normal BMACs with high glucose treatment. let-7f, a microRNA which has been related to endothelial angiogenic function, is found to play key role in TSP-2 increase, but let-7f did not directly interact with TSP-2 mRNA. Conclusions The upregulation of TSP-2 mediated by increased oxidative stress contributes to angiogenesis dysfunction in diabetic BMACs.
引用
收藏
页码:1920 / 1927
页数:8
相关论文
共 50 条
  • [31] A type 2 diabetes mellitus patient was successfully treated by autologous bone marrow-derived stem cell transplantation: A case report (vol 6, pg 2966, 2019)
    Phuong Thi-Bich Le
    Nguyen Phu-Van Doan
    Phan Van Tien
    Dang Ngo Chau Hoang
    Ngoc Kim Phan
    Phuc Van Pham
    BIOMEDICAL RESEARCH AND THERAPY, 2019, 6 (04): : 3141 - 3141
  • [32] Lipocalin-2-mediated upregulation of various antioxidants and growth factors protects bone marrow-derived mesenchymal stem cells against unfavorable microenvironments
    Raheleh Halabian
    Hossein Abdul Tehrani
    Ali Jahanian-Najafabadi
    Mehryar Habibi Roudkenar
    Cell Stress and Chaperones, 2013, 18 : 785 - 800
  • [33] Lipocalin 2 decreases senescence of bone marrow-derived mesenchymal stem cells under sub-lethal doses of oxidative stress
    Bahmani, Bahareh
    Roudkenar, Mehryar Habibi
    Halabian, Raheleh
    Jahanian-Najafabadi, Ali
    Amiri, Fatemeh
    Jalili, Mohammad Ali
    CELL STRESS & CHAPERONES, 2014, 19 (05): : 685 - 693
  • [34] Lipocalin 2 decreases senescence of bone marrow-derived mesenchymal stem cells under sub-lethal doses of oxidative stress
    Bahareh Bahmani
    Mehryar Habibi Roudkenar
    Raheleh Halabian
    Ali Jahanian-Najafabadi
    Fatemeh Amiri
    Mohammad Ali Jalili
    Cell Stress and Chaperones, 2014, 19 : 685 - 693
  • [35] Lipocalin-2-mediated upregulation of various antioxidants and growth factors protects bone marrow-derived mesenchymal stem cells against unfavorable microenvironments
    Halabian, Raheleh
    Tehrani, Hossein Abdul
    Jahanian-Najafabadi, Ali
    Roudkenar, Mehryar Habibi
    CELL STRESS & CHAPERONES, 2013, 18 (06): : 785 - 800
  • [36] Loss of Nrf2 in bone marrow-derived macrophages impairs antigen-driven CD8+ T cell function by limiting GSH and Cys availability
    Sha, Lisa K.
    Sha, Weixiao
    Kuchler, Laura
    Daiber, Andreas
    Giegerich, Annika K.
    Weigert, Andreas
    Knape, Tilo
    Snodgrass, Ryan
    Schroeder, Katrin
    Brandes, Ralf P.
    Bruene, Bernhard
    von Knethen, Andreas
    FREE RADICAL BIOLOGY AND MEDICINE, 2015, 83 : 77 - 88
  • [37] Bone marrow-derived mesenchymal stem cell transplantation ameliorates oxidative stress and restores intestinal mucosal permeability in chemically induced colitis in mice
    Sun, Tao
    Gao, Guang-Zhou
    Li, Rong-Fu
    Li, Xin
    Li, Da-Wei
    Wu, Shan-Shan
    Yeo, Anthony E. T.
    Jin, Bo
    AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH, 2015, 7 (05): : 891 - 901
  • [38] Oxidative Stress-Mediated Thombospondin-2 Upregulation Contributes to Diabetic Endothelial Progenitor Cell Dysfunction via Matrix Metalloproteinase-9 Activation
    Bae, Ok-Nam
    Chen, Alex F.
    CIRCULATION, 2008, 118 (18) : S457 - S458
  • [39] B Cell Lymphoma-2-Modified Bone Marrow-Derived Mesenchymal Stem Cells Transplantation for the Treatment of Diabetes Mellitus-Induced Erectile Dysfunction in a Rat Model
    Sun, Xiang
    Luo, Long-Hua
    Feng, Liang
    Li, Dong-Shui
    Zhong, Ke-Zhao
    UROLOGIA INTERNATIONALIS, 2017, 98 (03) : 358 - 366
  • [40] Infusion with Human Bone Marrow-derived Mesenchymal Stem Cells Improves β-cell Function in Patients and Non-obese Mice with Severe Diabetes
    Li, Lirong
    Hui, Hui
    Jia, Xiaolei
    Zhang, Jie
    Liu, Ying
    Xu, Qianyue
    Zhu, Dalong
    SCIENTIFIC REPORTS, 2016, 6