Focal overexpression of collagen IV characterizes the initiation of epithelial changes in polycystic kidney disease

Exp Nephrol. May-Jun 1994;2(3):190-5.


Changes of extracellular matrix are involved in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). The relationship between epithelial changes and extracellular matrix production was studied in a new rat model (Han:SPRD/cy+) at an early phase of cystogenesis. Messenger RNA expression of the alpha 1(IV)-chain of collagen type IV, the main structural component of basement membrane, was localized by in situ hybridization. The presence of collagen IV-protein was shown by immunohistochemistry. At an initial stage, cysts were lined with normal-appearing epithelium except for focal zones of less differentiated cells exhibiting strong collagen alpha 1(IV) mRNA expression and a thickened basement membrane. In these zones, an increase in cell number (2.39-fold) per unit epithelial area indicated hyperplastic growth. Conspicuously, these zones were found at 'bottleneck'-like transitions from normal-size tubules to cystic expansions. Intermediate stages of cysts showed more prominent extracellular matrix deposits and an overall maximally enhanced collagen IV mRNA expression, whereas terminal stages were lined with a flat, simplified epithelium and exhibited moderate collagen IV expression. We suggest that focally enhanced expression of collagen IV in the tubular epithelium and surrounding interstitium of Han:SPRD/cy+ rat kidney is initially involved in cyst development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basement Membrane / pathology
  • Collagen / genetics
  • Collagen / metabolism*
  • Epithelium / metabolism
  • Epithelium / pathology
  • Extracellular Matrix / pathology
  • Female
  • Gene Expression
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Kidney Tubules, Proximal / metabolism
  • Kidney Tubules, Proximal / pathology
  • Male
  • Polycystic Kidney, Autosomal Dominant / metabolism*
  • Polycystic Kidney, Autosomal Dominant / pathology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Mutant Strains
  • Rats, Sprague-Dawley


  • RNA, Messenger
  • Collagen