SiRNA Directed Against Annexin II Receptor Inhibits Angiogenesis via Suppressing MMP2 and MMP9 Expression

被引:25
作者
Song, Hongyuan [1 ]
Pan, Dongyan [1 ]
Sun, Weifeng [1 ]
Gu, Cao [1 ]
Zhang, Yuelu [1 ]
Zhao, Ping [2 ]
Qi, Zhongtian [2 ]
Zhao, Shihong [1 ]
机构
[1] Second Mil Univ, Changhai Hosp, Dept Ophthalmol, Shanghai 200433, Peoples R China
[2] Second Mil Univ, Dept Microbiol, Shanghai Key Lab Med Biodef, Shanghai 200433, Peoples R China
基金
中国国家自然科学基金;
关键词
Annexin II receptor; C5orf39; Angiogenesis; Matrix metalloproteinase; siRNA; NF-KAPPA-B; MATRIX METALLOPROTEINASES; APOPTOSIS; GROWTH; MIGRATION; ADHESION; INVASION; SYSTEM;
D O I
10.1159/000369745
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background/Aims: Annexin II receptor (AXIIR) is able to mediate Annexin II signal and induce apoptosis, but its role in angiogenesis remains unclear. This study tries to investigate the role of AXIIR in angiogenesis and the plausible molecular mechanism. Methods/Results: RNA interference technology was used to silence AXIIR, and the subsequent effects in vitro and in vivo were evaluated thereafter. Our data indicated that human umbilical vein endothelial cells (HUVECs) expressed AXIIR and knockdown of AXIIR significantly inhibited HUVECs proliferation, adhesion, migration, and tube formation in vitro and suppressed angiogenesis in vivo. Furthermore, AXIIR siRNA induced cell arrest in the S/G2 phase while had no effect on cell apoptosis. We found that these subsequent effects might be via suppressing the expression of matrix metalloproteinase 2and matrix metalloproteinase 9. Conclusion: AXIIR participates in angiogenesis, and may be a potential therapeutic target for angiogenesis related diseases. Copyright (C) 2015 S. Karger AG, Basel
引用
收藏
页码:875 / 884
页数:10
相关论文
共 31 条
[1]   Molecular regulation of angiogenesis and lymphangiogenesis [J].
Adams, Ralf H. ;
Alitalo, Kari .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2007, 8 (06) :464-478
[2]   Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways: novel insights into visfatin-induced angiogenesis [J].
Adya, Raghu ;
Tan, Bee K. ;
Punn, Anu ;
Chen, Jing ;
Randeva, Harpal S. .
CARDIOVASCULAR RESEARCH, 2008, 78 (02) :356-365
[3]   Nimbolide retards tumor cell migration, invasion, and angiogenesis by downregulating MMP-2/9 expression via inhibiting ERK1/2 and reducing DNA-binding activity of NF-κB in colon cancer cells [J].
Babykutty, Suboj ;
Priya, P. S. ;
Nandini, R. J. ;
Kumar, M. A. Suresh ;
Nair, Mangalam S. ;
Srinivas, Priya ;
Gopala, Srinivas .
MOLECULAR CARCINOGENESIS, 2012, 51 (06) :475-490
[4]  
Baumann K, 2014, NAT REV MOL CELL BIO, V15, P430
[5]   Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis [J].
Bergers, G ;
Brekken, R ;
McMahon, G ;
Vu, TH ;
Itoh, T ;
Tamaki, K ;
Tanzawa, K ;
Thorpe, P ;
Itohara, S ;
Werb, Z ;
Hanahan, D .
NATURE CELL BIOLOGY, 2000, 2 (10) :737-744
[6]   The Restriction Point of the Cell Cycle [J].
Blagosklonny, Mikhail V. ;
Pardee, Arthur B. .
CELL CYCLE, 2002, 1 (02) :103-110
[7]   Opinion - The role of apoptosis in cancer development and treatment response [J].
Brown, JM ;
Attardi, LD .
NATURE REVIEWS CANCER, 2005, 5 (03) :231-237
[8]   Angiogenesis in health and disease [J].
Carmeliet, P .
NATURE MEDICINE, 2003, 9 (06) :653-660
[9]   Molecular mechanisms and clinical applications of angiogenesis [J].
Carmeliet, Peter ;
Jain, Rakesh K. .
NATURE, 2011, 473 (7347) :298-307
[10]   Regulation of matrix metalloproteinases: An overview [J].
Chakraborti, S ;
Mandal, M ;
Das, S ;
Mandal, A ;
Chakraborti, T .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2003, 253 (1-2) :269-285