title: Primary cilia modulate balance of canonical and non-canonical Wnt signaling responses in the injured kidney.
abstract: BACKGROUND
  While kidney injury is associated with re-expression of numerous Wnt ligands and receptors, molecular mechanisms which underlie regulation of distinct Wnt signaling pathways and ensuing biological consequences remain incompletely understood. Primary cilia are increasingly being recognized as cellular 'antennae' which sense and transduce signals from the microenvironment, particularly through Wnt signaling. Here, we explored the role of cilia as modulators of canonical and non-canonical Wnt signaling activities involving tubular epithelial cells in the injured kidney.
  
  
  RESULTS
  We demonstrate that in the mouse model of unilateral ureter obstruction, progression of kidney injury correlates with increased expression of numerous Wnt ligands, and that increased expression of Wnt ligands corresponded with over-activation of canonical Wnt signaling. In contrast, non-canonical Wnt signaling dropped significantly during the course of kidney injury despite gradually increased expression of typical non-canonical and intermediate Wnt signaling ligands. We further demonstrate that in cultured tubular epithelial cells, cilia modulate balance between canonical and non-canonical signaling responses upon exposure to Wnt ligands.
  
  
  CONCLUSIONS
  We provide evidence that in the context of renal injury, primary cilia act as molecular switches between canonical and non-canonical Wnt signaling activity, possibly determining between regenerative and pro-fibrotic effects of Wnt re-expression in the injured kidney.
authors.affiliation: Department of Nephrology and Rheumatology, Göttingen University Medical Center, Georg August University, Robert-Koch Str. 40, 37075 Göttingen, Germany.
authors.forename: Shoji
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Nephrology and Rheumatology, Göttingen University Medical Center, Georg August University, Robert-Koch Str. 40, 37075 Göttingen, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Tampe
authors.affiliation: Department of Nephrology and Rheumatology, Göttingen University Medical Center, Georg August University, Robert-Koch Str. 40, 37075 Göttingen, Germany.
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Müller
authors.affiliation: Department of Nephrology and Rheumatology, Göttingen University Medical Center, Georg August University, Robert-Koch Str. 40, 37075 Göttingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Zeisberg
keywords: Cilia; Epithelial; Fibrosis