Renal injury is a third hit promoting rapid development of adult polycystic kidney disease

Hum Mol Genet. 2009 Jul 15;18(14):2523-31. doi: 10.1093/hmg/ddp147. Epub 2009 Apr 2.

Abstract

The 'two-hit' model is a widely accepted genetic mechanism for progressive cyst formation in autosomal dominant polycystic kidney disease. We have previously shown that adult inactivation of Pkd1 using the Mx1Cre(+) allele causes a late onset of focal cystic disease. An explanation for the delayed appearance of cysts is the requirement for an additional independent factor, or 'third hit'. Here we show that renal injury leads to massive cystic disease in the same mouse line. Cysts are labeled with a collecting duct/tubule marker, Lectin Dolichos biflorus Agglutinin, which correlates with the site of Cre-mediated recombination in the collecting system. 5-Bromo-2'-deoxyuridine labeling reveals that cyst-lining epithelial cells are comprised of regenerated cells in response to renal injury. These data demonstrate, for the first time, a role for polycystin-1 in kidney injury and repair and indicate that renal injury constitutes a 'third hit' resulting in rapid cyst formation in adulthood.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cysts / etiology
  • Cysts / metabolism
  • Cysts / pathology
  • Humans
  • Kidney / injuries*
  • Mice
  • Mice, Knockout
  • Polycystic Kidney, Autosomal Dominant / etiology*
  • Polycystic Kidney, Autosomal Dominant / genetics
  • Polycystic Kidney, Autosomal Dominant / metabolism
  • Polycystic Kidney, Autosomal Dominant / pathology
  • Reperfusion Injury / complications
  • TRPP Cation Channels / genetics
  • TRPP Cation Channels / metabolism

Substances

  • TRPP Cation Channels
  • polycystic kidney disease 1 protein