MicroRNA-92a Controls Angiogenesis and Functional Recovery of Ischemic Tissues in Mice

被引：1035

作者：

Bonauer, Angelika ^{[1
]}

Carmona, Guillaume ^{[1
]}

Iwasaki, Masayoshi ^{[1
]}

Mione, Marina ^{[2
]}

Koyanagi, Masamichi ^{[1
]}

Fischer, Ariane ^{[1
]}

Burchfield, Jana ^{[1
]}

Fox, Henrik ^{[1
,3
]}

Doebele, Carmen ^{[1
]}

Ohtani, Kisho ^{[1
]}

Chavakis, Emmanouil ^{[1
,3
]}

Potente, Michael ^{[1
,3
]}

Tjwa, Marc ^{[4
]}

Urbich, Carmen ^{[1
]}

Zeiher, Andreas M. ^{[3
]}

Dimmeler, Stefanie ^{[1
]}

机构：

[1] Univ Frankfurt, Ctr Mol Med, Inst Cardiovasc Regenerat, D-60590 Frankfurt, Germany

[2] Mol Oncol Fdn, Italian Fdn Canc Res Inst, I-02139 Milan, Italy

[3] Univ Frankfurt, Dept Med 3, Div Cardiol, D-60590 Frankfurt, Germany

[4] Univ Frankfurt, Leibniz AG, Inst Cardiovasc Regenerat, D-60590 Frankfurt, Germany

来源：

SCIENCE | 2009年 / 324卷 / 5935期

基金：

欧洲研究理事会;

关键词：

ENDOTHELIAL-CELL MIGRATION; VASCULAR INTEGRITY; EXPRESSION; DICER; FIBRONECTIN; POLYCISTRON; ALPHA(5); GENE;

D O I：

10.1126/science.1174381

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

MicroRNAs (miRs) are small noncoding RNAs that regulate gene expression by binding to target messenger RNAs (mRNAs), leading to translational repression or degradation. Here, we show that the miR-17 similar to 92 cluster is highly expressed in human endothelial cells and that miR-92a, a component of this cluster, controls the growth of new blood vessels (angiogenesis). Forced overexpression of miR-92a in endothelial cells blocked angiogenesis in vitro and in vivo. In mouse models of limb ischemia and myocardial infarction, systemic administration of an antagomir designed to inhibit miR-92a led to enhanced blood vessel growth and functional recovery of damaged tissue. MiR-92a appears to target mRNAs corresponding to several proangiogenic proteins, including the integrin subunit alpha5. Thus, miR-92a may serve as a valuable therapeutic target in the setting of ischemic disease.

引用

页码：1710 / 1713

页数：4

共 28 条

[1] MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].

Bartel, David P. .

CELL, 2007, 131 (04) :11-29

[2] Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5 [J].

Chen, Yun ;

Gorski, David H. .

BLOOD, 2008, 111 (03) :1217-1226

[3] Defective angiogenesis, endothelial migration, proliferation, and MAPK signaling in Rap1b-deficient mice [J].

Chrzanowska-Wodnicka, Magdalena ;

Kraus, Anna E. ;

Gale, Daniel ;

White, Gilbert C., II ;

VanSluys, Jillian .

BLOOD, 2008, 111 (05) :2647-2656

[4] Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster [J].

Dews, Michael ;

Homayouni, Asal ;

Yu, Duonan ;

Murphy, Danielle ;

Sevignani, Cinzia ;

Wentzel, Erik ;

Furth, Emma E. ;

Lee, William M. ;

Enders, Greg H. ;

T Mendell, Joshua ;

Thomas-Tikhonenko, Andrei .

NATURE GENETICS, 2006, 38 (09) :1060-1065

[5] MiR-126 regulates angiogenic signaling and vascular integrity [J].

Fish, Jason E. ;

Santoro, Massimo M. ;

Morton, Sarah U. ;

Yu, Sangho ;

Yeh, Ru-Fang ;

Wythe, Joshua D. ;

Lvey, Kathryn N. ;

Bruneau, Benoit G. ;

Stainier, Didier Y. R. ;

Srivastava, Deepak .

DEVELOPMENTAL CELL, 2008, 15 (02) :272-284

[6] Central roles of α5β1 integrin and fibronectin in vascular development in mouse embryos and embryoid bodies [J].

Francis, SE ;

Goh, KL ;

Hodivala-Dilke, K ;

Bader, BL ;

Stark, M ;

Davidson, D ;

Hynes, RO .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2002, 22 (06) :927-933

[7] MicroRNAs regulate brain morphogenesis in zebrafish [J].

Giraldez, AJ ;

Cinalli, RM ;

Glasner, ME ;

Enright, AJ ;

Thomson, JM ;

Baskerville, S ;

Hammond, SM ;

Bartel, DP ;

Schier, AF .

SCIENCE, 2005, 308 (5723) :833-838

[8] MicroRNA targeting specificity in mammals: Determinants beyond seed pairing [J].

Grimson, Andrew ;

Farh, Kyle Kai-How ;

Johnston, Wendy K. ;

Garrett-Engele, Philip ;

Lim, Lee P. ;

Bartel, David P. .

MOLECULAR CELL, 2007, 27 (01) :91-105

[9] A microRNA polycistron as a potential human oncogene [J].

He, L ;

Thomson, JM ;

Hemann, MT ;

Hernando-Monge, E ;

Mu, D ;

Goodson, S ;

Powers, S ;

Cordon-Cardo, C ;

Lowe, SW ;

Hannon, GJ ;

Hammond, SM .

NATURE, 2005, 435 (7043) :828-833

[10] Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase [J].

Imai, S ;

Armstrong, CM ;

Kaeberlein, M ;

Guarente, L .

NATURE, 2000, 403 (6771) :795-800

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