Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in myeloid cells

被引：228

作者：

Stefater, James A., III ^{[1
,2
,3
]}

Lewkowich, Ian ^{[4
]}

Rao, Sujata ^{[1
,2
,3
]}

Mariggi, Giovanni ^{[5
]}

Carpenter, April C. ^{[1
,2
]}

Burr, Adam R. ^{[6
]}

Fan, Jieqing ^{[1
,2
]}

Ajima, Rieko ^{[7
]}

Molkentin, Jeffery D. ^{[6
,8
]}

Williams, Bart O. ^{[9
]}

Wills-Karp, Marsha ^{[4
]}

Pollard, Jeffrey W. ^{[10
]}

Yamaguchi, Terry ^{[7
]}

Ferrara, Napoleone ^{[11
]}

Gerhardt, Holger ^{[5
,12
]}

Lang, Richard A. ^{[1
,2
]}

机构：

[1] Cincinnati Childrens Hosp, Visual Syst Grp, Div Pediat Ophthalmol, Med Ctr, Cincinnati, OH 45229 USA

[2] Cincinnati Childrens Hosp, Div Dev Biol, Med Ctr, Cincinnati, OH 45229 USA

[3] Univ Cincinnati, Dept Ophthalmol, Cincinnati, OH 45229 USA

[4] Cincinnati Childrens Hosp, Div Immunobiol, Med Ctr, Cincinnati, OH 45229 USA

[5] Canc Res UK, Vasc Biol Lab, London Res Inst, London WC2 3PX, England

[6] Univ Cincinnati, Div Mol Cardiovasc Biol, Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA

[7] NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA

[8] Univ Cincinnati, Med Ctr, Howard Hughes Med Inst, Cincinnati Childrens Hosp, Cincinnati, OH 45229 USA

[9] Van Andel Res Inst, Ctr Skeletal Dis Res, Grand Rapids, MI 49503 USA

[10] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY 10461 USA

[11] Genentech Inc, San Francisco, CA 94080 USA

[12] VIB, Vasc Patterning Lab, Vesalius Res Ctr, B-3000 Louvain, Belgium

来源：

NATURE | 2011年 / 474卷 / 7352期

关键词：

ENDOTHELIAL GROWTH-FACTOR; RETINAL NEOVASCULARIZATION; MOUSE; MECHANISM; VASCULATURE; MACROPHAGES; TUMORIGENESIS; HETEROGENEITY; INHIBITION; RECEPTOR-1;

D O I：

10.1038/nature10085

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：

Myeloid cells are a feature of most tissues. Here we show that during development, retinal myeloid cells (RMCs) produce Wnt ligands to regulate blood vessel branching. In the mouse retina, where angiogenesis occurs postnatally(1), somatic deletion in RMCs of the Wnt ligand transporter Wntless(2,3) results in increased angiogenesis in the deeper layers. We also show that mutation of Wnt5a and Wnt11 results in increased angiogenesis and that these ligands elicit RMC responses via a non-canonical Wnt pathway. Using cultured myeloid-like cells and RMC somatic deletion of Flt1, we show that an effector of Wnt-dependent suppression of angiogenesis by RMCs is Flt1, a naturally occurring inhibitor of vascular endothelial growth factor (VEGF)(4-6). These findings indicate that resident myeloid cells can use a non-canonical, Wnt-Flt1 pathway to suppress angiogenic branching.

引用

页码：511 / 515

页数：5

共 36 条

[1] Corneal avascularity is due to soluble VEGF receptor-1 [J].

Ambati, Balamurali K. ;

Nozaki, Miho ;

Singh, Nirbhai ;

Takeda, Atsunobu ;

Jani, Pooja D. ;

Suthar, Tushar ;

Albuquerque, Romulo J. C. ;

Richter, Elizabeth ;

Sakurai, Eiji ;

Newcomb, Michael T. ;

Kleinman, Mark E. ;

Caldwell, Ruth B. ;

Lin, Qing ;

Ogura, Yuichiro ;

Orecchia, Angela ;

Samuelson, Don A. ;

Agnew, Dalen W. ;

St. Leger, Judy ;

Green, W. Richard ;

Mahasreshti, Parameshwar J. ;

Curiel, David T. ;

Kwan, Donna ;

Marsh, Helene ;

Ikeda, Sakae ;

Leiper, Lucy J. ;

Collinson, J. Martin ;

Bogdanovich, Sasha ;

Khurana, Tejvir S. ;

Shibuya, Masabumi ;

Baldwin, Megan E. ;

Ferrara, Napoleone ;

Gerber, Hans-Peter ;

De Falco, Sandro ;

Witta, Jassir ;

Baffi, Judit Z. ;

Raisler, Brian J. ;

Ambati, Jayakrishna .

NATURE, 2006, 443 (7114) :993-997

[2] The Wingless homolog, WNT5A and its receptor Frizzled-5 regulate inflammatory responses of human mononuclear cells induced by microbial stimulation [J].

Blumenthal, Antje ;

Ehlers, Stefan ;

Lauber, Jorg ;

Buer, Jan ;

Lange, Christoph ;

Goldmann, Torsten ;

Heine, Holger ;

Brandt, Ernst ;

Reiling, Norbert .

BLOOD, 2006, 108 (03) :965-973

[3] The Extracellular Domain of Lrp5/6 Inhibits Noncanonical Wnt Signaling In Vivo [J].

Bryja, Vitezslav ;

Andersson, Emma R. ;

Schambony, Alexandra ;

Esner, Milan ;

Bryjova, Lenka ;

Biris, Kristin K. ;

Hall, Anita C. ;

Kraft, Bianca ;

Cajanek, Lukas ;

Yamaguchi, Terry P. ;

Buckingham, Margaret ;

Arenas, Ernest .

MOLECULAR BIOLOGY OF THE CELL, 2009, 20 (03) :924-936

[4] Generation of Mice with a Conditional Null Allele for Wntless [J].

Carpenter, April C. ;

Rao, Sujata ;

Wells, James M. ;

Campbell, Kenneth ;

Lang, Richard A. .

GENESIS, 2010, 48 (09) :554-558

[5] Differential expression of pro- and antiangiogenic factors in mouse strain-dependent hypoxia-induced retinal neovascularization [J].

Chan, CK ;

Pham, LN ;

Zhou, JH ;

Spee, C ;

Ryan, SJ ;

Hinton, DR .

LABORATORY INVESTIGATION, 2005, 85 (06) :721-733

[6] Mouse strain-dependent heterogeneity of resting limbal vasculature [J].

Chan, CK ;

Pham, LN ;

Chinn, C ;

Spee, C ;

Ryan, SJ ;

Akhurst, RJ ;

Hinton, DR .

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2004, 45 (02) :441-447

[7] Local Guidance of Emerging Vessel Sprouts Requires Soluble Flt-1 [J].

Chappell, John C. ;

Taylor, Sarah M. ;

Ferrara, Napoleone ;

Bautch, Victoria L. .

DEVELOPMENTAL CELL, 2009, 17 (03) :377-386

[8] A dedicated Wnt secretion factor [J].

Ching, Wendy ;

Nusse, Roel .

CELL, 2006, 125 (03) :432-433

[9] A Novel Mouse Model of Inflammatory Bowel Disease Links Mammalian Target of Rapamycin-Dependent Hyperproliferation of Colonic Epithelium to Inflammation-Associated Tumorigenesis [J].

Deng, Lin ;

Zhou, Jin-Feng ;

Sellers, Rani S. ;

Li, Jiu-Feng ;

Nguyen, Andrew V. ;

Wang, Yubao ;

Orlofsky, Amos ;

Liu, Qiang ;

Hume, David A. ;

Pollard, Jeffrey W. ;

Augenlicht, Leonard ;

Lin, Elaine Y. .

AMERICAN JOURNAL OF PATHOLOGY, 2010, 176 (02) :952-967

[10] Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction [J].

Fantin, Alessandro ;

Vieira, Joaquim M. ;

Gestri, Gaia ;

Denti, Laura ;

Schwarz, Quenten ;

Prykhozhij, Sergey ;

Peri, Francesca ;

Wilson, Stephen W. ;

Ruhrberg, Christiana .

BLOOD, 2010, 116 (05) :829-840

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