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Endoglin haploinsufficiency attenuates radiation-induced deterioration of kidney function in mice
Marion Scharpfenecker1, Ben Floot, Nicola S Russell
1Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Background And Purpose:
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.
Material And 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.
Insights
Mice with reduced endoglin levels (Eng(+/-)) show improved kidney function and less damage after irradiation compared to wild-type mice (Eng(+/+)). This suggests endoglin plays a key role in radiation-induced kidney injury.
Area of Science:
- Radiation oncology
- Vascular biology
- Renal pathophysiology
Background:
- Endoglin (CD105) is a TGF-β co-receptor critical for normal tissue damage.
- Reduced endoglin levels in Eng(+/-) mice lessen inflammation, vascular damage, and fibrosis post-irradiation.
- Previous studies indicate endoglin's role in radiation-induced tissue injury.
Purpose of the Study:
- To investigate if reduced endoglin levels in Eng(+/-) mice improve kidney function after irradiation.
- To assess the impact of endoglin deficiency on functional and histological kidney parameters post-radiation.
- To determine the protective effects of endoglin reduction against radiation-induced kidney damage.
Main Methods:
- Single dose of 14 Gy irradiation applied to kidneys of Eng(+/+) and Eng(+/-) mice.
- Functional kidney parameters (hematocrit, BUN) and histology analyzed at 20, 30, and 40 weeks post-irradiation.
- Assessment of vascular network integrity and myofibroblast markers (PDGFR-β).
Main Results:
- Eng(+/-) mice exhibited improved kidney function (hematocrit, BUN) at 40 weeks post-irradiation compared to Eng(+/+) mice.
- Irradiation damaged the vascular network and increased PDGFR-β positive cells in Eng(+/+) kidneys.
- Eng(+/-) mice showed preserved vascular perfusion and reduced PDGFR-β cells, which did not worsen after irradiation.
Conclusions:
- Reduced endoglin levels protect against radiation-induced kidney damage.
- Eng(+/-) mice demonstrate superior kidney function and morphology post-irradiation compared to Eng(+/+) mice.
- Endoglin deficiency confers protection against late normal tissue damage in the kidneys.
