Kidney Res Clin Pract.  2024 May;43(3):313-325. 10.23876/j.krcp.23.087.

High water intake induces primary cilium elongation in renal tubular cells

• Kong MJ
• Han SJ
• Seu SY
• Han KH
• Lipschutz JH
• Park KM

• KMID: 2557314
• DOI: http://doi.org/10.23876/j.krcp.23.087

Abstract

Background
The primary cilium protrudes from the cell surface and functions as a mechanosensor. Recently, we found that water intake restriction shortens the primary cilia of renal tubular cells, and a blockage of the shortening disturbs the ability of the kidneys to concentrate urine. Here, we investigate whether high water intake (HWI) alters primary cilia length, and if so, what is its underlying mechanism and its role on kidney urine production. Methods: Experimental mice were given free access to normal water (normal water intake) or 3% sucrose-containing water for HWI for 2 days. Some mice were administered with U0126 (10 mg/kg body weight), an inhibitor of MEK kinase, from 2 days before HWI, daily. The primary cilium length and urine amount and osmolality were investigated. Results: HWI-induced diluted urine production and primary cilium elongation in renal tubular cells. HWI increased the expression of α-tubulin acetyltransferase 1 (αTAT1), leading to the acetylation of α-tubulins, a core protein of the primary cilia. HWI also increased phosphorylated ERK1/2 (p-ERK1/2) and exocyst complex component 5 (Exoc5) expression in the kidneys. U0126 blocked HWI-induced increases in αTAT1, p-ERK1/2, and Exoc5 expression. U0126 inhibited HWI-induced α-tubulin acetylation, primary cilium elongation, urine amount increase, and urine osmolality decrease. Conclusion: These results show that increased water intake elongates the primary cilia via ERK1/2 activation and that ERK inhibition prevents primary cilium elongation and diluted urine production. These data suggest that the elongation of primary cilium length is associated with the production of diluted urine.

Keyword

α-tubulin acetyltransferase; Aquaporin 2; ERK; Hydration; Primary cilia