Fluid shear stress increases transepithelial transport of Ca2+ in ciliated distal convoluted and connecting tubule cells [Research]

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 (DCT and CNT, 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 DCT/CNT, 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.

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