title: Fluid shear stress increases transepithelial transport of Ca2+in ciliated distal convoluted and connecting tubule cells.
abstract: In kidney, transcellular transport of Ca2+is mediated by transient receptor potential vanilloid 5 and Na+-Ca2+exchanger 1 proteins in distal convoluted and connecting tubules (DCTs and CNTs, respectively). It is not yet understood how DCT/CNT cells can adapt to differences in tubular flow rate and, consequently, Ca2+load. This study aims to elucidate the molecular mechanisms by which DCT/CNT cells sense fluid dynamics to control transepithelial Ca2+reabsorption and whether their primary cilia play an active role in this process. Mouse primary DCT/CNT cultures were subjected to a physiologic fluid shear stress (FSS) of 0.12 dyn/cm2Transient receptor potential vanilloid 5 and Na+-Ca2+exchanger 1 mRNA levels were significantly increased upon FSS exposure compared with static controls. Functional studies with45Ca2+demonstrated a significant stimulation of transepithelial Ca2+transport under FSS compared with static conditions. Primary cilia removal decreased Ca2+transport in both static and FSS conditions, a finding that correlated with decreased expression of genes involved in transepithelial Ca2+transport; however, FSS-induced stimulation of Ca2+transport was still observed. These results indicate that nephron DCT and CNT segments translate FSS into a physiologic response that implicates an increased Ca2+reabsorption. Moreover, primary cilia influence transepithelial Ca2+transport in DCTs/CNTs, yet this process is not distinctly coupled to FSS sensing by these organelles.-Mohammed, S. G., Arjona, F. J., Latta, F., Bindels, R. J. M., Roepman, R., Hoenderop, J. G. J. Fluid shear stress increases transepithelial transport of Ca2+in ciliated distal convoluted and connecting tubule cells.
authors.affiliation: Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Sami G
authors.initials: SG
authors.lastname: Mohammed
authors.affiliation: Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Arjona
authors.affiliation: Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Femke
authors.initials: F
authors.lastname: Latta
authors.affiliation: Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: René J M
authors.initials: RJM
authors.lastname: Bindels
authors.affiliation: Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Roepman
authors.affiliation: Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; joost.hoenderop@radboudumc.nl.
authors.forename: Joost G J
authors.initials: JGJ
authors.lastname: Hoenderop
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D017136:Ion Transport / Q000502:physiology; D007668:Kidney / Q000378:metabolism; D051379:Mice; D033081:Shear Strength / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D013312:Stress, Physiological; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D019831:Sodium-Calcium Exchanger; D050916:TRPV Cation Channels; C110374:sodium-calcium exchanger 1; D012964:Sodium; D002118:Calcium
keywords: Ca2+ reabsorption; mechanosensation; primary cilia; renal tubules