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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 \u03b1-tubulin, a core protein of microtubules. Results: WD decreased urine output and increased urine osmolality, concomitant with apical plasma membrane localization of aquaporin 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 decreased. WD induced deacetylation of \u03b1-tubulin without altering \u03b1-tubulin levels in the kidney. Tubastatin prevented the shortening of cilia through increasing HDAC6 activity and consequently increasing acetylated \u03b1-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 \u03b1-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. <\/jats:p>","DOI":"10.23876\/j.krcp.22.274","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T04:01:15Z","timestamp":1685505675000},"page":"312-324","update-policy":"https:\/\/doi.org\/10.23876\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Shortening of primary cilia length is associated with urine concentration in the kidneys"],"prefix":"10.23876","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9684-2373","authenticated-orcid":true,"given":"Min Jung","family":"Kong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5425-9056","authenticated-orcid":true,"given":"Sang 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