Hyperglycemia in the absence of cilia accelerates cystogenesis and induces renal damage

Am J Physiol Renal Physiol. 2015 Jul 1;309(1):F79-87. doi: 10.1152/ajprenal.00652.2014. Epub 2015 Apr 22.


In polycystic kidney disease (PKD), the rate of cyst formation and disease progression is highly variable. The lack of predictability in disease progression may be due to additional environmental factors or pathophysiological processes called "third hits." Diabetes is a growing epidemic, and recent studies suggest that PKD patients may be at an increased risk for this disease. We sought to determine if hyperglycemia enhances the initiation and rate of cystogenesis. Tamoxifen was administered to adult Ift88 conditional floxed allele mice to induce cilia loss in the presence of Cre. Subsequent administration of streptozotocin resulted in equivalent hyperglycemia in cilia(+) and cilia(-) mice. Hyperglycemia with loss of cilia increased the rate of cyst formation and cell proliferation. Structural and functional alterations in the kidney, including focal glomerular foot process effacement, interstitial inflammation, formation of primitive renal tubules, polyuria, and increased proteinuria, were also observed in hyperglycemic cilia(-) mice. Gene array analysis indicated enhanced Wnt and epithelial-to-mesenchymal transition signaling in the kidney of hyperglycemic cilia(-) mice. These data show that hyperglycemia, in the absence of cilia, results in renal structural and functional damage and accelerates cystogenesis, suggesting that diabetes is a risk factor in the progression of PKD.

Keywords: Wnt; diabetes; epithelial-to-mesenchymal transition; polycystic kidney disease; streptozotocin.

Publication types

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

MeSH terms

  • Animals
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition
  • Female
  • Hemodynamics
  • Hyperglycemia / complications*
  • Hyperglycemia / pathology
  • Hyperglycemia / physiopathology
  • Kidney / pathology*
  • Kidney Function Tests
  • Male
  • Mice, Knockout
  • Polycystic Kidney Diseases / etiology*
  • Polycystic Kidney Diseases / pathology
  • Random Allocation
  • Wnt Proteins / metabolism


  • Wnt Proteins