Endoglin haploinsufficiency attenuates radiation-induced deterioration of kidney function in mice.

Abstract

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. 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. 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. Taken together, we show that not only kidney morphology, but also kidney function is improved after irradiation in Eng(+/-) compared to Eng(+/+) mice.