Morphological alterations of primary cilia in renal tubules of a rat model of polycystic kidney disease

 

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https://storage.unitedwebnetwork.com/files/1099/b37d601f073bd0be21356ba0030a44f2.pdf
Morphological alterations of primary cilia in renal tubules of a rat model of polycystic kidney disease

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Kanako
Kumamoto
Kanako Kumamoto kumamoto@fujita-hu.ac.jp Fujita Health University Research Promotion Headquarters, Advanced medical research center for animal models of Human disease Toyoake Japan *
Hiroyuki Kagami kagami@med.nagoya-cu.ac.jp Nagoya City University Graduate School of Nursing Nagoya Japan -
Sei Saitoh saitoh@fujita-hu.ac.jp Fujita Health University Department of Disease Systems Analysis Medicine Toyoake Japan -
Shiori Yamada shiori.anluv@gmail.com Fujita Health University Research Promotion Headquarters, Advanced medical research center for animal models of Human disease Toyoake Japan - Yamaguchi Ladies Clinic Clinic Nagoya Japan
Mami Matsumoto m.mami@med.nagoya-cu.ac.jp National Institute for Physiological Sciences Section of Electron Microscopy, Supportive Center for Brain Research Okazaki Japan - Nagoya City University Department of Developmental and Regenerative Neurobiology Institute of Brain Science Nagoya Japan
Nobuhiko Ohno nohno@nips.ac.jp National Institute of Physiological Sciences Division of Ultrastructural Research Okazaki Japan - Jichi Medical University Department of Anatomy, Division of Histology and Cell Biology Shimotsuke Japan
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Polycystic kidney disease (PKD) is an inherited disorder characterized by progressive cyst formation in renal tubules, leading to renal failure. Primary cilia, projecting into the tubular lumen, act as mechanochemical sensors that detect urinary flow and extracellular signals such as Hedgehog, Wnt, and PDGF. Structural changes of cilia may therefore alter the mechanical forces they experience and their sensory function. This study aimed to characterize the morphology and ultrastructure of primary cilia in collecting duct cells of PCK rats, a model of autosomal recessive PKD.

Kidneys were collected from PCK rats and age-matched Sprague-Dawley controls. Samples were analyzed by hematoxylin-eosin staining and immunofluorescence, and primary cilia were visualized using confocal microscopy and serial block-face scanning electron microscopy. Ciliary length, curvature, and ultrastructural features were quantified. Statistical comparisons were performed using ANOVA with post hoc tests; P < 0.05 was considered significant.

Primary cilia in dilated collecting ducts of PCK rats were significantly longer and more curved than those in controls (P < 0.05). Ultrastructural examination confirmed alterations consistent with these morphological changes. Mechanical stress along a cilium depends on its length and curvature; therefore, mathematical analysis suggests that these structural differences may influence how cilia senses mechanical and chemical cues within the tubular environment.

In PCK rats, primary cilia exhibit abnormal elongation and curvature, suggesting that altered morphology may affect the mechanical forces they experience. These findings highlight that morphological remodeling of cilia, as interpreted through a mathematical approach, may contribute to impaired sensory function in PKD.

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