Kidney injury molecule-1 expression in murine polycystic kidney disease

Am J Physiol Renal Physiol. 2002 Dec;283(6):F1326-36. doi: 10.1152/ajprenal.00166.2002. Epub 2002 Jul 24.

Abstract

Kidney injury molecule-1 (Kim-1) is a type 1 membrane protein maximally upregulated in proliferating and dedifferentiated tubular cells after renal ischemia. Because epithelial dedifferentiation, proliferation, and local ischemia may play a role in the pathophysiology of autosomal dominant polycystic kidney disease, we investigated Kim-1 expression in a mouse model of this disease. In the Pkd2(WS25/-) mouse model for autosomal dominant polycystic kidney disease, cystic kidneys show markedly upregulated Kim-1 levels compared with noncystic control kidneys. Kim-1 is present in a subset of cysts of different sizes and segmental origins and in clusters of proximal tubules near cysts. Kim-1-expressing tubular cells show decreased complexity and quantity of basolateral staining for Na-K-ATPase. Other changes in polarity characteristic of ischemic injury are not present in Kim-1-expressing pericystic tubules. Polycystin-2 expression is preserved in Kim-1-expressing tubules. The interstitium surrounding Kim-1-expressing tubules shows high proliferative activity and staining for smooth muscle alpha-actin, characteristic of myofibroblasts. Although the functional role of the protein in cysts remains unknown, Kim-1 expression in tubules is strongly associated with partial dedifferentiation of epithelial cells and may play a role in the development of interstitial fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Division
  • Epithelial Cells / metabolism
  • Fibroblasts / pathology
  • Immunohistochemistry
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology
  • Membrane Proteins / metabolism
  • Mice
  • Molecular Sequence Data
  • Muscle, Smooth / pathology
  • Polycystic Kidney, Autosomal Dominant / metabolism*
  • Reference Values
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Staining and Labeling
  • TRPP Cation Channels
  • Tissue Distribution

Substances

  • Cell Adhesion Molecules
  • Havcr1protein, rat
  • Membrane Proteins
  • TRPP Cation Channels
  • polycystic kidney disease 2 protein
  • Sodium-Potassium-Exchanging ATPase