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Shortening of primary cilia length is associated with urine concentration in the kidneys
- Title
- Shortening of primary cilia length is associated with urine concentration in the kidneys
- Authors
- Kong M.J.; Han S.J.; Seu S.Y.; Han K.-H.; Lipschutz J.H.; Park K.M.
- Ewha Authors
- 한기환
- SCOPUS Author ID
- 한기환
- Issue Date
- 2023
- Journal Title
- Kidney Research and Clinical Practice
- ISSN
- 2211-9132
- Citation
- Kidney Research and Clinical Practice vol. 42, no. 3, pp. 312 - 324
- Keywords
- Aquaporin 2; Histone deacetylase 6; Osmolality; Primary cilia; Water deprivation
- Publisher
- The Korean Society of Nephrology
- Indexed
- SCIE; SCOPUS; KCI
- Document Type
- Article
- Abstract
- Background: The primary cilium, a microtubule-based cellular organelle present in certain kidney cells, functions as a mechano-sen-sor to monitor fluid flow in addition to various other biological functions. In kidneys, the primary cilia protrude into the tubular lumen and are directly exposed to pro-urine flow and components. However, their effects on urine concentration remain to be defined. Here, we investigated the association between primary cilia and urine concentration. Methods: Mice either had free access to water (normal water intake, NWI) or were not allowed access to water (water deprivation, WD). Some mice received tubastatin, an inhibitor of histone deacetylase 6 (HDAC6), which regulates the acetylation of α-tubulin, a core protein of microtubules. Results: WD decreased urine output and increased urine osmolality, concomitant with apical plasma membrane localization of aqua-porin 2 (AQP2) in the kidney. After WD, compared with after NWI, the lengths of primary cilia in renal tubular epithelial cells were shortened and HDAC6 activity increased. WD induced deacetylation of α-tubulin without altering α-tubulin levels in the kidney. Tubas-tatin prevented the shortening of cilia through increasing HDAC6 activity and consequently increasing acetylated α-tubulin expression. Furthermore, tubastatin prevented the WD-induced reduction of urine output, urine osmolality increase, and apical plasma membrane localization of AQP2. Conclusions: WD shortens primary cilia length through HDAC6 activation and α-tubulin deacetylation, while HDAC6 inhibition blocks the WD-induced changes in cilia length and urine output. This suggests that cilia length alterations are involved, at least in part, in the regulation of body water balance and urine concentration. © 2023 by The Korean Society of Nephrology.
- DOI
- 10.23876/j.krcp.22.274
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
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