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

Kelli M. Sas, Hong Yin, Wayne R. Fitzgibbon, Catalin F. Baicu, Michael R. Zile, Stacy L. Steele, May Amria, Takamitsu Saigusa, Jason Funk, Marlene A. Bunni, Gene P. Siegal, Brian J. Siroky, John Bissler, P. Darwin Bell

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)F79-F87
JournalAmerican Journal of Physiology - Renal Physiology
Volume309
Issue number1
DOIs
StatePublished - Jul 6 2015

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Cilia
Hyperglycemia
Kidney
Polycystic Kidney Diseases
Obese Mice
Disease Progression
Cysts
Polyuria
Epithelial-Mesenchymal Transition
Tamoxifen
Streptozocin
Proteinuria
Foot
Alleles
Cell Proliferation
Inflammation
Genes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

Cite this

Sas, K. M., Yin, H., Fitzgibbon, W. R., Baicu, C. F., Zile, M. R., Steele, S. L., ... Bell, P. D. (2015). Hyperglycemia in the absence of cilia accelerates cystogenesis and induces renal damage. American Journal of Physiology - Renal Physiology, 309(1), F79-F87. https://doi.org/10.1152/ajprenal.00652.2014

Hyperglycemia in the absence of cilia accelerates cystogenesis and induces renal damage. / Sas, Kelli M.; Yin, Hong; Fitzgibbon, Wayne R.; Baicu, Catalin F.; Zile, Michael R.; Steele, Stacy L.; Amria, May; Saigusa, Takamitsu; Funk, Jason; Bunni, Marlene A.; Siegal, Gene P.; Siroky, Brian J.; Bissler, John; Bell, P. Darwin.

In: American Journal of Physiology - Renal Physiology, Vol. 309, No. 1, 06.07.2015, p. F79-F87.

Research output: Contribution to journalArticle

Sas, KM, Yin, H, Fitzgibbon, WR, Baicu, CF, Zile, MR, Steele, SL, Amria, M, Saigusa, T, Funk, J, Bunni, MA, Siegal, GP, Siroky, BJ, Bissler, J & Bell, PD 2015, 'Hyperglycemia in the absence of cilia accelerates cystogenesis and induces renal damage', American Journal of Physiology - Renal Physiology, vol. 309, no. 1, pp. F79-F87. https://doi.org/10.1152/ajprenal.00652.2014
Sas, Kelli M. ; Yin, Hong ; Fitzgibbon, Wayne R. ; Baicu, Catalin F. ; Zile, Michael R. ; Steele, Stacy L. ; Amria, May ; Saigusa, Takamitsu ; Funk, Jason ; Bunni, Marlene A. ; Siegal, Gene P. ; Siroky, Brian J. ; Bissler, John ; Bell, P. Darwin. / Hyperglycemia in the absence of cilia accelerates cystogenesis and induces renal damage. In: American Journal of Physiology - Renal Physiology. 2015 ; Vol. 309, No. 1. pp. F79-F87.
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