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Acute kidney injury and aberrant planar cell polarity induce cyst formation in mice lacking renal cilia.

Human molecular genetics | Jun 1, 2008

http://www.ncbi.nlm.nih.gov/pubmed/18263895

Polycystic kidney disease (PKD) is an inherited disorder that is characterized by the accumulation of cysts in the renal parenchyma and progressive decline in renal function. Recent studies suggest that PKD arises from abnormalities of the primary cilium. We have previously shown that kidney-specific inactivation of the ciliogenic gene Kif3a during embryonic development produces kidney cysts and renal failure. Here, we used tamoxifen-inducible, kidney-specific gene targeting to inactivate Kif3a in the postnatal mouse kidney. Kidney-specific inactivation of Kif3a in newborn mice resulted in the loss of primary cilia and produced kidney cysts primarily in the loops of Henle, whereas inactivation in adult mice did not lead to the rapid development of cysts despite a comparable loss of primary cilia. The age-dependence and locations of the cysts suggested that cyst formation required increased rates of cell proliferation. To test this possibility, we stimulated cell proliferation in the adult kidney by inducing acute kidney injury and tubular regeneration. Acute kidney injury induced cyst formation in adult Kif3a mutant mice. Analysis of pre-cystic tubules in Kif3a mutant mice showed that the loss of cilia did not stimulate cell proliferation but instead resulted in aberrant planar cell polarity as manifested by abnormalities in the orientation of cell division. We conclude that primary cilia are required for the maintenance of planar cell polarity in the mammalian kidney and that acute kidney injury exacerbates cystic disease.

Pubmed ID: 18263895 RIS Download

Mesh terms: Acute Disease | Animals | Cell Polarity | Cilia | Cysts | Humans | Kidney Diseases | Kinesin | Loop of Henle | Mice | Mice, Transgenic | Polycystic Kidney Diseases

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Associated grants

  • Agency: NIDDK NIH HHS, Id: P30 DK079310
  • Agency: NIDDK NIH HHS, Id: P30 DK079328
  • Agency: NIDDK NIH HHS, Id: P30 DK079328-01
  • Agency: NIDDK NIH HHS, Id: P30DK079328
  • Agency: NIDDK NIH HHS, Id: P50 DK057328
  • Agency: NIDDK NIH HHS, Id: P50DK057328
  • Agency: NIDDK NIH HHS, Id: R01 DK067565
  • Agency: NIDDK NIH HHS, Id: R01 DK067565-05
  • Agency: NIDDK NIH HHS, Id: R01DK67565
  • Agency: NIDDK NIH HHS, Id: R37 DK042921
  • Agency: NIDDK NIH HHS, Id: T32 DK007257
  • Agency: NIDDK NIH HHS, Id: T32 DK007257-20
  • Agency: NIDDK NIH HHS, Id: T32DK007257

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