Macrophage Wnt7b is critical for kidney repair and regeneration

被引：353

作者：

Lin, Shuei-Liong ^{[3
,4
,5
]}

Li, Bing ^{[3
,4
]}

Rao, Sujata ^{[1
,2
,6
]}

Yeo, Eun-Jin ^{[1
,2
,6
]}

Hudson, Thomas E. ^{[3
,4
]}

Nowlin, Brian T. ^{[3
,4
]}

Pei, Huaying ^{[3
,4
]}

Chen, Lijun ^{[7
]}

Zheng, Jie J. ^{[7
]}

Carroll, Thomas J. ^{[8
]}

Pollard, Jeffrey W. ^{[9
]}

McMahon, Andrew P. ^{[10
]}

Lang, Richard A. ^{[1
,2
,6
]}

Duffield, Jeremy S. ^{[3
,4
]}

机构：

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

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

[3] Brigham & Womens Hosp, Dept Med, Div Renal, Inflammat Res Lab, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Boston, MA 02115 USA

[5] Natl Taiwan Univ Hosp, Dept Med, Taipei 100, Taiwan

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

[7] St Jude Childrens Res Hosp, Dept Biol Struct, Memphis, TN 38105 USA

[8] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dept Mol Biol, Dallas, TX 75390 USA

[9] Yeshiva Univ Albert Einstein Coll Med, Dept Mol & Dev Biol, Bronx, NY 10461 USA

[10] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 09期

基金：

美国国家卫生研究院;

关键词：

macrophage; repair; regeneration; kidney; canonical Wnt pathway; EPITHELIAL-CELLS; INJURY; PROGRESSION; ACTIVATION; MECHANISM; RECEPTOR; LRP5;

D O I：

10.1073/pnas.0912228107

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：

Macrophages are required for tissue homeostasis through their role in regulation of the immune response and the resolution of injury. Here we show, using the kidney as a model, that the Wnt pathway ligand Wnt7b is produced by macrophages to stimulate repair and regeneration. When macrophages are inducibly ablated from the injured kidney, the canonical Wnt pathway response in kidney epithelial cells is reduced. Furthermore, when Wnt7b is somatically deleted in macrophages, repair of injury is greatly diminished. Finally, injection of the Wnt pathway regulator Dkk2 enhances the repair process and suggests a therapeutic option. Because Wnt7b is known to stimulate epithelial responses during kidney development, these findings suggest that macrophages are able to rapidly invade an injured tissue and reestablish a developmental program that is beneficial for repair and regeneration.

引用

页码：4194 / 4199

页数：6

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