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Reduction the Length of the Primary Cilia by 1-Indanone Suppressed Renal Cysts Development in ADPKD
40 Pages Posted: 9 Dec 2021
More...Abstract
Cyst development in polycystic kidney disease (PKD) involves abnormal epithelial cell proliferation, which is believed to be affected by the primary cilia mediated signal transduction in the epithelial cells. Herein is reported that a natural compound 1-Indanone retard cyst development in in vitro and in vivo models of PKD, including MDCK cyst model, embryonic kidney cyst model, and a neonatal, kidney-specific Pkd1 knockout mouse model. It was found 1-Indanone significantly inhibited the abnormal elongation of cystic epithelial cilia by promoting tubulin polymerization and down-regulating expression of anterograde transport motor protein KIF3A and IFT88. 1-Indanone down-regulated ciliary coordinated WNT/β-catenin, Hedgehog signaling remarkably. The experimental results indicate that 1-Indanone inhibited cystic cell proliferation by reducing abnormally prolonged cilia length in cystic epithelial cells, which suggests that 1-Indanone may hold therapeutic potential to reduce cyst development in PKD. And reducing primary cilia length will become a potent strategy for ADPKD treatment.
Funding Information: This work was supported by the National Natural Science Foundation of
356 China grants [81974083, 81620108029, 81330074, 81873597 and 81800388], the Beijing
357 Natural Science Foundation grant [7212151]
Declaration of Interests: All the authors declared no competing interests.
Ethics Approval Statement: All animal experiments were approved by the relevant government authorities and ethics committees, in compliance with the local regulations for the care and use of laboratory animals. All animal experiments were approved by the Care and Use of Laboratory Animals of China Association for Laboratory Animal Science, in compliance with the Institutional Animal Care and Use Committee at the Peking University Health Science Center (26 Febrary 2021; protocol no. LA2021080).
Keywords: ADPKD, Cysts, 1-Indanone, Primary cilia
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