Shortening of primary cilia length is associated with urine concentration in the kidneys
Background The primary cilium, a microtubule-based cellular organelle present in certain kidney cells, functions as a mechano-sensor 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-...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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The Korean Society of Nephrology
2023-05-01
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| Series: | Kidney Research and Clinical Practice |
| Subjects: | |
| Online Access: | http://www.krcp-ksn.org/upload/pdf/j-krcp-22-274.pdf |
| _version_ | 1797692908873187328 |
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| author | Min Jung Kong Sang Jun Han Sung Young Seu Ki-Hwan Han Joshua H. Lipschutz Kwon Moo Park |
| author_facet | Min Jung Kong Sang Jun Han Sung Young Seu Ki-Hwan Han Joshua H. Lipschutz Kwon Moo Park |
| author_sort | Min Jung Kong |
| collection | DOAJ |
| description | Background The primary cilium, a microtubule-based cellular organelle present in certain kidney cells, functions as a mechano-sensor 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 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 increased. WD induced deacetylation of α-tubulin without altering α-tubulin levels in the kidney. Tubastatin 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. |
| first_indexed | 2024-03-12T02:34:21Z |
| format | Article |
| id | doaj.art-f9a58959fef543a2b0a76b3424c9898b |
| institution | Directory Open Access Journal |
| issn | 2211-9132 2211-9140 |
| language | English |
| last_indexed | 2024-03-12T02:34:21Z |
| publishDate | 2023-05-01 |
| publisher | The Korean Society of Nephrology |
| record_format | Article |
| series | Kidney Research and Clinical Practice |
| spelling | doaj.art-f9a58959fef543a2b0a76b3424c9898b2023-09-05T01:23:54ZengThe Korean Society of NephrologyKidney Research and Clinical Practice2211-91322211-91402023-05-0142331232410.23876/j.krcp.22.2746224Shortening of primary cilia length is associated with urine concentration in the kidneysMin Jung Kong0Sang Jun Han1Sung Young Seu2Ki-Hwan Han3Joshua H. Lipschutz4Kwon Moo Park5 Department of Anatomy, BK21 Plus, Cardiovascular Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea Department of Anatomy, BK21 Plus, Cardiovascular Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea Department of Anatomy, BK21 Plus, Cardiovascular Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea Department of Anatomy, Ewha Womans University School of Medicine, Seoul, Republic of Korea Department of Medicine, Medical University of South Carolina, Charleston, SC, USA Department of Anatomy, BK21 Plus, Cardiovascular Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of KoreaBackground The primary cilium, a microtubule-based cellular organelle present in certain kidney cells, functions as a mechano-sensor 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 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 increased. WD induced deacetylation of α-tubulin without altering α-tubulin levels in the kidney. Tubastatin 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.http://www.krcp-ksn.org/upload/pdf/j-krcp-22-274.pdfprimary ciliaaquaporin 2histone deacetylase 6osmolalitywater deprivation |
| spellingShingle | Min Jung Kong Sang Jun Han Sung Young Seu Ki-Hwan Han Joshua H. Lipschutz Kwon Moo Park Shortening of primary cilia length is associated with urine concentration in the kidneys Kidney Research and Clinical Practice primary cilia aquaporin 2 histone deacetylase 6 osmolality water deprivation |
| title | Shortening of primary cilia length is associated with urine concentration in the kidneys |
| title_full | Shortening of primary cilia length is associated with urine concentration in the kidneys |
| title_fullStr | Shortening of primary cilia length is associated with urine concentration in the kidneys |
| title_full_unstemmed | Shortening of primary cilia length is associated with urine concentration in the kidneys |
| title_short | Shortening of primary cilia length is associated with urine concentration in the kidneys |
| title_sort | shortening of primary cilia length is associated with urine concentration in the kidneys |
| topic | primary cilia aquaporin 2 histone deacetylase 6 osmolality water deprivation |
| url | http://www.krcp-ksn.org/upload/pdf/j-krcp-22-274.pdf |
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