title: Role of atrophic changes in proximal tubular cells in the peritubular deposition of type IV collagen in a rat renal ablation model.
abstract: 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 beta, alpha-smooth muscle actin (alpha-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 alpha-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.
authors.affiliation: University of Shizuoka, School of Nursing, 52-1, Yada, Shizuoka, Shizuoka-ken, 422-8526, Japan. kimura@u-shizuoka-ken.ac.jp
authors.forename: Masato
authors.initials: M
authors.lastname: Kimura
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Asano
authors.forename: Katsushige
authors.initials: K
authors.lastname: Abe
authors.forename: Masanobu
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Akira
authors.initials: A
authors.lastname: Hishida
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001284:Atrophy; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism*; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology*; D008297:Male; D023421:Models, Animal; D009130:Muscle, Smooth / Q000378:metabolism; D009392:Nephrectomy; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D015843:Serpins / Q000378:metabolism
chemical_list: D000199:Actins; D024141:Collagen Type IV; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C494662:Serpinh1 protein, rat; D015843:Serpins; D020797:Receptor, Platelet-Derived Growth Factor beta