title: Endoglin haploinsufficiency attenuates radiation-induced deterioration of kidney function in mice.
abstract: OBJECTIVE
  Endoglin is a transforming growth receptor beta (TGF-β) co-receptor, which plays a crucial role in the development of late normal tissue damage. Mice with halved endoglin levels (Eng(+/-) mice) develop less inflammation, vascular damage and fibrosis after kidney irradiation compared to their wild type littermates (Eng(+/+) mice). This study was aimed at investigating whether reduced tissue damage in Eng(+/-) mice also results in superior kidney function.
  
  
  METHODS
  Kidneys of Eng(+/+) and Eng(+/-) mice were irradiated with a single dose of 14 Gy. Functional kidney parameters and kidney histology were analysed at 20, 30 and 40 weeks after irradiation.
  
  
  RESULTS
  Eng(+/-) mice displayed improved kidney parameters (haematocrit, BUN) compared to Eng(+/+) mice at 40 weeks after irradiation. Irradiation of Eng(+/+) kidneys damaged the vascular network and led to an increase in PDGFR-β positive cells, indicative of fibrosis-promoting myofibroblasts. Compared to Eng(+/+) kidneys, vascular perfusion and number of PDGFR-β positive cells were reduced in Eng(+/-) control mice; however, this did not further deteriorate after irradiation.
  
  
  CONCLUSIONS
  Taken together, we show that not only kidney morphology, but also kidney function is improved after irradiation in Eng(+/-) compared to Eng(+/+) mice.
authors.affiliation: Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: m.scharpfenecker@nki.nl.
authors.forename: Marion
authors.initials: M
authors.lastname: Scharpfenecker
authors.forename: Ben
authors.initials: B
authors.lastname: Floot
authors.forename: Nicola S
authors.initials: NS
authors.lastname: Russell
authors.forename: Rob P
authors.initials: RP
authors.lastname: Coppes
authors.forename: Fiona A
authors.initials: FA
authors.lastname: Stewart
mesh_terms: D000818:Animals; D000071063:Endoglin; D057895:Haploinsufficiency; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007668:Kidney / Q000473:pathology / Q000502:physiology / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D017263:Technetium Tc 99m Mertiatide; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D017263:Technetium Tc 99m Mertiatide
keywords: Endoglin; Fibrosis; Kidney; Perfusion; Pericytes; Vasculature