Fluid shear stress increases transepithelial transport of Ca2+ in ciliated distal convoluted and connecting tubule cells. Issue 5 (18th January 2017)

• Record Type: Journal Article
• Authors: Mohammed, Sami G.; Arjona, Francisco J.; Latta, Femke; Bindels, René J. M.; Roepman, Ronald; Hoenderop, Joost G. J.
• Is Part Of: FASEB journal. Volume 31:Issue 5(2017)
• Page Start: 1796
• Page End: 1806
• Publication Date: 2017-01-18
• Subjects: renal tubules -- mechanosensation -- primary cilia -- Ca2+ reabsorption; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201600687RRR
• Languages: English
• ISSNs: 0892-6638

Abstract

ABSTRACT: In kidney, transcellular transport of Ca 2+ is mediated by transient receptor potential vanilloid 5 and Na + ‐Ca 2+ 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, Ca 2+ load. This study aims to elucidate the molecular mechanisms by which DCT/CNT cells sense fluid dynamics to control transepithelial Ca 2+ 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/cm 2 . Transient receptor potential vanilloid 5 and Na + ‐Ca 2+ exchanger 1 mRNA levels were significantly increased upon FSS exposure compared with static controls. Functional studies with 45 Ca 2+ demonstrated a significant stimulation of transepithelial Ca 2+ transport under FSS compared with static conditions. Primary cilia removal decreased Ca 2+ transport in both static and FSS conditions, a finding that correlated with decreased expression of genes involved in transepithelial Ca 2+ transport; however, FSS‐induced stimulation of Ca 2+ transport was still observed. These results indicate that nephron DCT and CNT segments translate FSS into a physiologic response that implicates an increased Ca 2+ reabsorption. Moreover, primary cilia influence transepithelial Ca 2+ 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. FASEB J. 31, 1796–1806 (2017). www.fasebj.org