Tubular epithelial cells in the kidney are characterized by primary cilia. It has been shown that cilia act as mechanosensor in vitro, increasing calcium influx into the cell upon changes in fluid shear stress induced on apical cell membrane by perfusion. On the basis of these observations it has been postulated that in patients affected by polycystic kidney disease the mechanosensing of tubular cell cilia is impaired by mutation in the protein polycystin. It is not yet clear how this tubular cell dysfuction is responsible for initiation and progression of cyst formation. Here we studied the effect of laminar fluid shear stress upon MDCK-II cells, a cell line of tubular kidney epithelium. We used a parallel plate flow chamber to apply controlled laminar fluid shear stress in vitro. Control MDCK-II cell monolayers were maintained in static culture condition. Seven days after reaching confluence, MDCK-II cell monolayers in conventional static culture developed dome structures, elevating from culture plate, as observed at scanning electron microscopy. Exposure to shear stress of 3 dynes/cm_2 for 6 hours in the perfusion chamber induced rearrangement of cell structure with disappearance of cell domes and formation of tubular structures. This phenomenon was completely absent in monolayers exposed to shear stress in the presence of EGTA, a calcium chelating agent. These data indicate that tubular cell structure and function may be modulated by tubular fluid flow rate in kidney tubules. Elucidation of the mechanisms responsible for cell adaptation to shear stress may open new insights on the pathophysiofcjgy of polycystic kidney disease, a progressive kidney disease that has no effective cure so far.
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