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Primary cilia control the maturation of tubular lumen in renal collecting duct epithelium

Sougoumarin, Soushma
Published in American journal of physiology. Cell physiology. 2017, vol. 313, no. 1, p. C94-C107
Abstract The key role of the primary cilium in developmental processes is illustrated by ciliopathies resulting from genetic defects of its components. Ciliopathies include a large variety of dysmorphic syndromes that share in common the presence of multiple kidney cysts. These observations suggest that primary cilia may control morphogenetic processes in the developing kidney. In this study, we assessed the role of primary cilium in branching tubulogenesis and/or lumen development using kidney collecting duct-derived mCCDN21 cells that display spontaneous tubulogenic properties when grown in collagen-Matrigel matrix. Tubulogenesis and branching were not altered when cilium body growth was inhibited by Kif3A or Ift88 silencing. In agreement with the absence of a morphogenetic effect, proliferation and wound-healing assay revealed that neither cell proliferation nor migration were altered by cilium body disruption. The absence of cilium following Kif3A or Ift88 silencing in mCCDN21 cells did not alter the initial stages of tubular lumen generation while lumen maturation and enlargement were delayed. This delay in tubular lumen maturation was not observed after Pkd1 knockdown in mCCDN21 cells. The delayed lumen maturation was explained by neither defective secretion or increased reabsorption of luminal fluid. Our results indicate that primary cilia do not control early morphogenetic processes in renal epithelium. Rather, primary cilia modulate tubular lumen maturation and enlargement resulting from luminal fluid accumulation in tubular structures derived from collecting duct cells.
Keywords AnimalsCell MovementCell ProliferationCilia/metabolismCollagen/chemistryDrug CombinationsGene Expression RegulationDevelopmentalIon TransportKidney TubulesCollecting/cytology/metabolismKinesin/antagonists & inhibitors/genetics/metabolismLaminin/chemistryMicePodocytes/cytology/metabolismPrimary Cell CultureProtein Kinase C/antagonists & inhibitors/genetics/metabolismProteoglycans/chemistryRNASmall Interfering/genetics/metabolismSignal TransductionTumor Suppressor Proteins/antagonists & inhibitors/genetics/metabolism
PMID: 28468945
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Article (Published version) (4 MB) - document accessible for UNIGE members only Limited access to UNIGE
Research group Laboratoire de physiologie et pathophysiologie des cellules rénales (29)
Swiss National Science Foundation: 310030_143929
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ERNANDEZ, Thomas et al. Primary cilia control the maturation of tubular lumen in renal collecting duct epithelium. In: American Journal of Physiology. Cell Physiology, 2017, vol. 313, n° 1, p. C94-C107. doi: 10.1152/ajpcell.00290.2016 https://archive-ouverte.unige.ch/unige:98733

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Deposited on : 2017-11-08

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