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(American Journal of Pathology. 2001;158:75-85.)
© 2001 American Society for Investigative Pathology


Regular Articles

Role of Atrophic Tubules in Development of Interstitial Fibrosis in Microembolism-Induced Renal Failure in Rat

Takayuki Suzuki*, Masato Kimura{dagger}, Mitsuko Asano{dagger}, Yoshihide Fujigaki* and Akira Hishida*

From the First Department of Medicine,*
Hamamatsu University School of Medicine, Hamamatsu; and the School of Nursing,{dagger}
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 {alpha}-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 {alpha}-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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