NDT Advance Access originally published online on May 3, 2005
Nephrology Dialysis Transplantation 2005 20(8):1559-1565; doi:10.1093/ndt/gfh872
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Role of atrophic changes in proximal tubular cells in the peritubular deposition of type IV collagen in a rat renal ablation model
1 University of Shizuoka, School of Nursing, Shizuoka, Shizuoka, Japan, 2 Nagasaki University School of Medicine, The Second Department of Medicine, Nagasaki, Nagasaki, Japan and 3 Hamamatsu University School of Medicine, The First Department of Medicine, Hamamatsu, Shizuoka, Japan
Correspondence and offprint requests to: Masato Kimura, University of Shizuoka, School of Nursing, 52-1, Yada, Shizuoka, Shizuoka-ken, 422-8526, Japan. Email: kimura{at}u-shizuoka-ken.ac.jp
Background. Tubular atrophy, dilation and interstitial fibrosis are common in tubulointerstitial lesions, but the precise roles and inter-relationships of these components in the development of interstitial lesions have not been determined. This study focused on the origin and roles of atrophic tubules in the peritubular deposition of type IV collagen in a rat renal ablation model.
Methods. Male Wistar rats underwent 5/6 nephrectomy or sham operation, and then were sacrificed at 4, 8 or 12 weeks, their remaining kidneys removed for histological and immuno-histochemical studies as well as in situ hybridization for type IV collagen mRNA.
Results. Immuno-histochemistry demonstrated the positive staining of atrophic tubules to vimentin, platelet-derived growth factor-B chain (PDGF) and heat shock protein 47 (HSP47). Cells positive to one or more of PDGF receptor ß, 
-smooth muscle actin (-SMA), and HSP47 accumulated around atrophic tubules. Type IV collagen was also increased in the proximity of the atrophic tubules. These intimate relationships were more clearly demonstrated in ‘mosaic tubules’, which are composed of both intact and atrophic proximal tubular epithelial cells, and which had a mixed pattern of staining with vimentin, PDGF and HSP47. The interstitial cells positive to -SMA or HSP47, or both, were in close contact with atrophic but not with intact epithelial cells. Type IV collagen was exclusively deposited between atrophic tubules and HSP47-positive interstitial cells. In situ hybridization of type IV collagen mRNA demonstrated predominant expression in atrophic tubular epithelial cells, but not in surrounding interstitial cells.
Conclusions. These findings suggest that atrophic proximal tubular cells are active in the development of collagen deposition in the peritubular space, i.e. in this model type IV collagen in the interstitial fibrotic area may be produced mainly by atrophic proximal tubules.
Keywords: atrophic tubule; -smooth muscle actin (-SMA); fibroblast; interstitial fibrosis; platelet-derived growth factor (PDGF); renal ablation
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