The role of the tubulointerstitium in radiation-induced renal fibrosis.

Abstract:

:The functional and morphological response of the remaining hypertrophied kidney in unilaterally nephrectomized rats to single doses of 0-20 Gy X rays was investigated. Functional and histological end points were assessed serially 4-24 weeks postirradiation. Renal irradiation led to time- and dose-dependent reductions in renal function, seen in terms of a decreased glomerular filtration rate, increased blood urea nitrogen, and reduced hematocrit. These changes were accompanied by morphological changes in the glomerular, tubular and interstitial portions of the kidney. However, dose-dependent changes were observed only in terms of tubulointerstitial lesions. Significant increases in the degree of interstitial staining for collagen type III and fibronectin were observed 24 weeks postirradiation. These increases in extracellular matrix components were accompanied by a significant increase in interstitial alpha smooth muscle actin, suggesting activation of interstitial fibroblasts into myofibroblasts. There was no evidence of glomerular Tgfb after renal irradiation. A significant increase in tubular Tgfb staining was only seen 8 weeks postirradiation. In contrast, there was a shift of staining to the interstitium such that by 24 weeks postirradiation interstitial Tgfb staining was significantly greater than that seen in controls. These findings suggest that the tubule epithelial cell and the interstitial fibroblast are both active participants in the development and/or progression of radiation-induced renal fibrosis.

journal_name

Radiat Res

journal_title

Radiation research

authors

Robbins ME,O'Malley Y,Zhao W,Davis CS,Bonsib SM

doi

10.1667/0033-7587(2001)155[0481:trotti]2.0.co;2

subject

Has Abstract

pub_date

2001-03-01 00:00:00

pages

481-9

issue

3

eissn

0033-7587

issn

1938-5404

journal_volume

155

pub_type

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