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/cm² Transient receptor potential vanilloid 5 and Na⁺-Ca²⁺ exchanger 1 mRNA levels were significantly increased upon FSS exposure compared with static controls. Functional studies with ⁴⁵Ca²⁺ 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.

Keywords: Ca2+ reabsorption; mechanosensation; primary cilia; renal tubules.