Disappearance of the angiogenic potential of endothelial cells caused by Argonaute2 knockdown

被引:41
作者
Asai, Tomohiro [1 ]
Suzuki, Yuko [1 ]
Matsushita, Saori [1 ]
Yonezawa, Sei [1 ]
Yokota, Junichi [1 ]
Katanasaka, Yasufumi [1 ]
Ishida, Tatsuhiro [2 ]
Dewa, Takehisa [3 ]
Kiwada, Hiroshi [2 ]
Nango, Mamoru [3 ]
Oku, Naoto [1 ]
机构
[1] Univ Shizuoka, Sch Pharmaceut Sci, Dept Med Biochem & Global COE, Suruga Ku, Shizuoka 4228526, Japan
[2] Univ Tokushima, Dept Pharmacokinet & Biopharmaceut, Inst Hlth Biosci, Tokushima 7708505, Japan
[3] Nagoya Inst Technol, Showa Ku, Nagoya, Aichi 4668555, Japan
关键词
Argonaute2; angiogenesis; siRNA; polycation liposomes;
D O I
10.1016/j.bbrc.2008.01.074
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Argonaute2 (Ago2), a component protein of RNA-induced silencing complex, plays a central role in RNA interference. We focused on the involvement of Ago2 in angiogenesis. Human umbilical vein endothelial cells (HUVECs) stimulated with several growth factors such as vascular endothelial growth factor were used for angiogenesis assays. We applied polycation liposomes for transfection of small interfering RNA (siRNA) to determine the biological effects of siRNA for Ago2 (siAgo2) on HUVECs. The proliferation study indicated that siAgo2 significantly suppressed the growth of HUVECs compared with control siRNA. TUNEL staining showed a certain population of HUVECs treated with siAgo2 underwent apoptosis. Furthermore, the treatment with siAgo2 suppressed the tube formation of HUVECs and significantly reduced the length of the tubes. These present data demonstrate that siAgo2 inhibited indispensable events of angiogenesis in vitro. This is the first report suggesting that Ago2 is required for angiogenesis. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:243 / 248
页数:6
相关论文
共 17 条
[1]   Angiogenesis modulation in cancer research: Novel clinical approaches [J].
Cristofanilli, M ;
Charnsangavej, C ;
Hortobagyi, GN .
NATURE REVIEWS DRUG DISCOVERY, 2002, 1 (06) :415-426
[2]   Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells [J].
Elbashir, SM ;
Harborth, J ;
Lendeckel, W ;
Yalcin, A ;
Weber, K ;
Tuschl, T .
NATURE, 2001, 411 (6836) :494-498
[3]   Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy [J].
Ferrara, N ;
Hillan, KJ ;
Novotny, W .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 333 (02) :328-335
[4]   Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans [J].
Fire, A ;
Xu, SQ ;
Montgomery, MK ;
Kostas, SA ;
Driver, SE ;
Mello, CC .
NATURE, 1998, 391 (6669) :806-811
[5]  
Gregory RI, 2005, CELL, V123, P631, DOI 10.1016/j.cell.2005.10.022
[6]   Argonaute2 is the catalytic engine of mammalian RNAi [J].
Liu, JD ;
Carmell, MA ;
Rivas, FV ;
Marsden, CG ;
Thomson, JM ;
Song, JJ ;
Hammond, SM ;
Joshua-Tor, L ;
Hannon, GJ .
SCIENCE, 2004, 305 (5689) :1437-1441
[7]   Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes [J].
Matranga, C ;
Tomari, Y ;
Shin, C ;
Bartel, DP ;
Zamore, PD .
CELL, 2005, 123 (04) :607-620
[8]  
Meister G, 2004, MOL CELL, V15, P185, DOI 10.1016/j.molcel.2004.07.007
[9]   Distinct roles for argonaute proteins in small RNA-directed RNA cleavage pathways [J].
Okamura, K ;
Ishizuka, A ;
Siomi, H ;
Siomi, MC .
GENES & DEVELOPMENT, 2004, 18 (14) :1655-1666
[10]   A novel non-viral gene transfer system, polycation liposomes [J].
Oku, N ;
Yamazaki, Y ;
Matsuura, M ;
Sugiyama, M ;
Hasegawa, M ;
Nango, M .
ADVANCED DRUG DELIVERY REVIEWS, 2001, 52 (03) :209-218