Related Experiment Video
Updated: May 31, 2026
Mouse Model of Acute to Chronic Kidney Disease Transition Induced by Renal Ischemia/Reperfusion Injury
Published on: February 10, 2026
ALK1 heterozygosity delays development of late normal tissue damage in the irradiated mouse kidney
Marion Scharpfenecker1, Ben Floot, Regina Korlaar
1Department of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Background And Purpose:
Activin receptor-like kinase 1 (ALK1) is a transforming growth factor β (TGF-β) receptor, which is mainly expressed in endothelial cells regulating proliferation and migration in vitro and angiogenesis in vivo. Endothelial cells also express the co-receptor endoglin, which modulates ALK1 effects on endothelial cells. Our previous studies showed that mice with reduced endoglin levels develop less irradiation-induced vascular damage and fibrosis, caused by an impaired inflammatory response. This study was aimed at investigating the role of ALK1 in late radiation toxicity.
Material And Methods:
Kidneys of ALK(+/+) and ALK1(+/-) mice were irradiated with 14 Gy. Mice were sacrificed at 10, 20, and 30 weeks after irradiation and gene expression and protein levels were analyzed.
Results:
Compared to wild type littermates, ALK1(+/-) mice developed less inflammation and fibrosis at 20 weeks after irradiation, but displayed an increase in pro-inflammatory and pro-fibrotic gene expression at 30 weeks. In addition, ALK1(+/-) mice showed superior vascular integrity at 10 and 20 weeks after irradiation which deteriorated at 30 weeks coinciding with changes in the VEGF pathway.
Conclusions:
ALK1(+/-) mice develop a delayed normal tissue response by modulating the inflammatory response and growth factor expression after irradiation.
Insights
Reduced levels of activin receptor-like kinase 1 (ALK1) in mice delayed radiation-induced inflammation and fibrosis. However, this protective effect diminished over time, indicating a complex role for ALK1 in normal tissue response to irradiation.
Area of Science:
- Molecular biology
- Cell biology
- Radiation oncology
Background:
- Activin receptor-like kinase 1 (ALK1), a TGF-β receptor, is crucial for endothelial cell function.
- Endoglin, a co-receptor, modulates ALK1 activity.
- Previous research linked reduced endoglin to decreased radiation-induced vascular damage and fibrosis.
Purpose of the Study:
- To investigate the role of ALK1 in the development of late radiation toxicity.
- To understand ALK1's contribution to radiation-induced normal tissue damage.
Main Methods:
- Irradiation of wild-type (ALK+/+) and ALK1(+/-) mice kidneys with 14 Gy.
- Analysis of gene and protein expression at 10, 20, and 30 weeks post-irradiation.
Main Results:
- ALK1(+/-) mice exhibited reduced inflammation and fibrosis at 20 weeks post-irradiation.
- Pro-inflammatory and pro-fibrotic gene expression increased in ALK1(+/-) mice at 30 weeks.
- Vascular integrity was superior in ALK1(+/-) mice at 10 and 20 weeks, deteriorating by 30 weeks, linked to VEGF pathway changes.
Conclusions:
- Mice with reduced ALK1 levels show a delayed normal tissue response to irradiation.
- ALK1 modulates inflammatory responses and growth factor expression following radiation exposure.
