Translator Disclaimer
1 February 2009 Radiation-Induced Activation of TGF-β Signaling Pathways in Relation to Vascular Damage in Mouse Kidneys
Author Affiliations +
Abstract

Kruse, J. J. C. M., Floot, B. G. J., Te Poele, J. A. M., Russell, N. S. and Stewart, F. A. Radiation-Induced Activation of TGF-β Signaling Pathways in Relation to Vascular Damage in Mouse Kidneys. Radiat. Res. 171, 188–197 (2009).

The purpose of this study was to investigate the long-term effects of radiation-induced alterations in TGF-β signaling pathways with respect to the development of vascular damage in the irradiated kidney. Total RNA was isolated from mouse kidneys at 1–30 weeks after irradiation, and quantitative real-time PCR analyses were performed for TGF-β receptors (ALK1, ALK5, endoglin), downstream mediators (Smad7, CTGF), and downstream targets (PAI-1 and Id-1). Expression of endoglin and Smad7 protein as well as nucleo-cytoplasmic distribution of phospho Smad 2/3 and phospho Smad 1/5 was analyzed by immunohistochemistry. Radiation caused a rapid and persistent increase in expression of TGF-β receptors and mediators from 1–30 weeks after treatment. Expression of Id-1, a downstream target of endothelial cell specific receptor ALK1, was transiently increased (1–10 weeks after irradiation) but returned to control levels at later times. Expression of PAI-1, a downstream target of ALK5, increased progressively from 10–30 weeks after irradiation. These results show that radiation activated TGF-β signaling pathways in the kidney and shifted the balance in favor of ALK5 signaling, which generally inhibits endothelial cell proliferation and migration. We hypothesize that prolonged activation of ALK5 signaling and relative suppression of ALK1 signaling may provide an explanation for the telangiectatic phenotype observed in irradiated kidneys.

Jacqueline J. C M. Kruse, Ben G. J. Floot, Johannes A. M. te Poele, Nicola S. Russell, and Fiona A. Stewart "Radiation-Induced Activation of TGF-β Signaling Pathways in Relation to Vascular Damage in Mouse Kidneys," Radiation Research 171(2), 188-197, (1 February 2009). https://doi.org/10.1667/RR1526.1
Received: 14 July 2008; Accepted: 1 September 2008; Published: 1 February 2009
JOURNAL ARTICLE
10 PAGES


SHARE
ARTICLE IMPACT
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top