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From the First Department of Medicine,*
Hamamatsu
University School of Medicine, Hamamatsu; and the School of
Nursing,
University of Shizuoka,
Shizuoka, Japan
We explored the origin and participation of atrophic tubules in the
progression of interstitial fibrosis using a new microembolic rat model
of chronic renal failure in which foci of atrophic tubules with
cufflike basement membrane thickening developed at 4 weeks. Atrophic
tubules, immunoreactive for vimentin and platelet-derived
growth factor, were surrounded by transformed interstitial
cells expressing platelet-derived growth factor receptor ß and
-smooth muscle actin. Some tubules in the deep cortex and the outer
stripe of the outer medulla had a mosaic appearance. Tall,
intact proximal tubular cells with a brush border and positivity for
Phaseolus vulgaris erythroagglutinin, adjoined
typical atrophic tubule cells having no brush border and an
immunostaining pattern characteristic for atrophic tubules. The
transformed interstitial cells expressing
-smooth muscle actin were
located near atrophic but not intact tubular epithelial cells. Type IV
collagen accumulated between damaged tubular cells and transformed
interstitial cells. Heat shock protein 47 showed immunoreactivity in
damaged epithelial cells and in interstitial myofibroblasts. Staining
with an anti-endothelial antibody suggested damage to peritubular
capillaries near atrophic tubules. By disturbance of microcirculation
following microsphere injection, proximal tubular cells
expressed vimentin and platelet-derived growth factor; diffusion of the
latter presumably stimulated transformation of interstitial cells to
myofibroblasts. Injured tubular epithelial cells and interstitial
myofibroblasts both were responsible for interstitial
fibrosis.
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H. T. Yu Progression of Chronic Renal Failure Arch Intern Med, June 23, 2003; 163(12): 1417 - 1429. [Abstract] [Full Text] [PDF] |
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