title: Endoglin haploinsufficiency reduces radiation-induced fibrosis and telangiectasia formation in mouse kidneys.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Department of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors: Marion
authors: M
authors: Scharpfenecker
authors: Ben
authors: B
authors: Floot
authors: Nicola S
authors: NS
authors: Russell
authors: Peter
authors: P
authors: Ten Dijke
authors: Fiona A
authors: FA
authors: Stewart
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D000071063:Endoglin; D005260:Female; D005355:Fibrosis / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation; D006238:Haploidy; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007668:Kidney / Q000473:pathology / Q000528:radiation effects*; D007678:Kidney Glomerulus / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000235:genetics* / Q000378:metabolism; D011839:Radiation, Ionizing; D011897:Random Allocation; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013684:Telangiectasis / Q000235:genetics* / Q000473:pathology
chemical_list: D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta