Endoglin haploinsufficiency reduces radiation-induced fibrosis and telangiectasia formation in mouse kidneys

被引：40

作者：

Scharpfenecker, Marion ^{[1
]}

Floot, Ben ^{[1
]}

Russell, Nicola S. ^{[2
]}

ten Dijke, Peter ^{[3
,4
]}

Stewart, Fiona A. ^{[1
]}

机构：

[1] Netherlands Canc Inst, Dept Expt Therapy, Amsterdam, Netherlands

[2] Netherlands Canc Inst, Dept Radiotherapy, Amsterdam, Netherlands

[3] Leiden Univ, Med Ctr, Dept Mol Cell Biol, Leiden, Netherlands

[4] Leiden Univ, Med Ctr, Ctr Biomed Genet, Leiden, Netherlands

来源：

RADIOTHERAPY AND ONCOLOGY | 2009年 / 92卷 / 03期

关键词：

Endoglin; Irradiation; TGF-beta; Telangiectasia; Fibrosis; HHT; GROWTH-FACTOR-BETA; HEREDITARY HEMORRHAGIC TELANGIECTASIA; BINDING-PROTEIN; ARTERIOVENOUS-MALFORMATIONS; CELL-PROLIFERATION; ENDOTHELIAL-CELLS; UP-REGULATION; EXPRESSION; FIBROBLASTS; COLLAGEN;

D O I：

10.1016/j.radonc.2009.06.013

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background and purpose: Endoglin is a transforming growth factor beta (TGF-beta) co-receptor mainly expressed in dividing endothelial cells. It regulates cell proliferation and survival and is upregulated at sites of vessel repair. Mutations in endoglin have been linked to the vascular disease hereditary hemorrhagic telangiectasia (HHT). HHT patients display dilated capillaries (telangiectasia) that are prone to rupture, Cancer patients receiving radiotherapy develop similar vascular damage in normal tissues lying in the irradiation field. If located in the mucosa, irradiation-induced telangiectasia can lead to severe bleeding. Therefore, this study was aimed at investigating the role of endoglin in radiation-induced telangiectasia formation. Materials and methods: Kidneys of endoglin heterozygous (Eng(+/-)) or wild type mice were irradiated with 16 Gy. Mice were sacrificed after 20 weeks and changes in gene expression and protein levels were analysed. Results: Expression of TGF-beta target genes involved in radiation-induced fibrosis and fibrosis development in the kidney decreased in Eng(+/-) compared to wild type mice. Unexpectedly, Eng(+/-) mice also displayed reduced telangiectasia formation in the irradiated kidney. Conclusions: Endoglin plays an important role in the development of irradiation-induced normal tissue damage. Future studies will show whether interfering with endoglin functions protects tissues from late radiation toxicity. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 92 (2009) 484-491

引用

页码：484 / 491

页数：8

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