Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

1-Indanone retards cyst development in ADPKD mouse model by stabilizing tubulin and down-regulating anterograde transport of cilia

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. Cyst development in ADPKD involves abnormal epithelial cell proliferation, which is affected by the primary cilia-mediated signal transduction in the epithelial cells. Thus, primary cilium has been considered as a therapeutic target for ADPKD. Since ADPKD exhibits many pathological features similar to solid tumors, we investigated whether targeting primary cilia using anti-tumor agents could alleviate the development of ADPKD. Twenty-four natural compounds with anti-tumor activity were screened in MDCK cyst model, and 1-Indanone displayed notable inhibition on renal cyst growth without cytotoxicity. This compound also inhibited cyst development in embryonic kidney cyst model. In neonatal kidney-specific Pkd1 knockout mice, 1-Indanone remarkably slowed down kidney enlargement and cyst expansion. Furthermore, we demonstrated that 1-Indanone inhibited the abnormal elongation of cystic epithelial cilia by promoting tubulin polymerization and significantly down-regulating expression of anterograde transport motor protein KIF3A and IFT88. Moreover, we found that 1-Indanone significantly down-regulated ciliary coordinated Wnt/β-catenin, Hedgehog signaling pathways. These results demonstrate that 1-Indanone inhibits cystic cell proliferation by reducing abnormally prolonged cilia length in cystic epithelial cells, suggesting that 1-Indanone may hold therapeutic potential to retard cyst development in ADPKD.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: 1-Indanone is identified as an inhibitor of renal cysts.
Fig. 2: 1-Indanone suppresses cyst expansion in PKD mice.
Fig. 3: 1-Indanone retards cyst progression dose-dependently.
Fig. 4: 1-Indanone inhibits abnormal cell proliferation in PKD mice.
Fig. 5: 1-Indanone reduces the primary cilium length of renal tubular epithelium in PKD mice.
Fig. 6: 1-Indanone retards primary cilia prolongation with FSK stimulation in mIMCD cells.
Fig. 7: 1-Indanone modulates the structure of primary cilia by stabilizing tubulin.
Fig. 8: 1-Indanone down-regulates anterograde transport of primary cilia.
Fig. 9: 1-Indanone down-regulates signaling pathways coordinated with primary cilia.
Fig. 10: The diagram of mechanism in which 1-Indanone delays cyst development in ADPKD.

References

  1. Cornec-Le Gall E, Alam A, Perrone RD. Autosomal dominant polycystic kidney disease. Lancet. 2019;393:919–35.

    PubMed  Article  Google Scholar 

  2. Bergmann C, Guay-Woodford LM, Harris PC, Horie S, Peters DJM, Torres VE. Polycystic kidney disease. Nat Rev Dis Prim. 2018;4:50.

    PubMed  Article  Google Scholar 

  3. Dong K, Zhang C, Tian X, Coman D, Hyder F, Ma M, et al. Renal plasticity revealed through reversal of polycystic kidney disease in mice. Nat Genet. 2021;53:1649–63.

    CAS  PubMed  Article  Google Scholar 

  4. Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet. 2007;369:1287–301.

    PubMed  Article  Google Scholar 

  5. Torres VE, Harris PC. Progress in the understanding of polycystic kidney disease. Nat Rev Nephrol. 2019;15:70–2.

    PubMed  PubMed Central  Article  Google Scholar 

  6. Yoder BK, Hou X, Guay-Woodford LM. The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia. J Am Soc Nephrol. 2002;13:2508–16.

    CAS  PubMed  Article  Google Scholar 

  7. Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, et al. Polycystins 1 and 2 mediate mechano-sensation in the primary cilium of kidney cells. Nat Genet. 2003;33:129–37.

    CAS  PubMed  Article  Google Scholar 

  8. Fliegauf M, Benzing T, Omran H. When cilia go bad: cilia defects and ciliopathies. Nat Rev Mol Cell Biol. 2007;8:880–93.

    CAS  PubMed  Article  Google Scholar 

  9. Bergmann C, Guay-Woodford LM, Harris PC, Horie S, Peters DJM, Torres VE. Polycystic kidney disease. Nat Rev Dis Prim. 2018;4:50.

    PubMed  Article  Google Scholar 

  10. Cloutier M, Manceur AM, Guerin A, Aigbogun MS, Oberdhan D, Gauthier M. The societal economic burden of autosomal dominant polycystic kidney disease in the United States. BMC Health Serv Res. 2020;20:126.

    PubMed  PubMed Central  Article  Google Scholar 

  11. Chapman AB, Devuyst O, Eckardt KU, Gansevoort RT, Harris T, Horie S, et al. Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a kidney disease: Improving global outcomes (KDIGO) controversies conference. Kidney Int. 2015;88:17–27.

    PubMed  PubMed Central  Article  Google Scholar 

  12. Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Perrone RD, Koch G, et al. REPRISE Trial Investigators. Tolvaptan in later-stage autosomal dominant polycystic kidney disease. N Engl J Med. 2017;377:1930–42.

    CAS  PubMed  Article  Google Scholar 

  13. Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, et al. TEMPO 3:4 Trial Investigators. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012;367:2407–18.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  14. Torres VE, Gansevoort RT, Perrone RD, Chapman AB, Ouyang J, Lee J, et al. Tolvaptan in ADPKD patients with very low kidney function. Kidney Int Rep. 2021;6:2171–8.

    PubMed  PubMed Central  Article  Google Scholar 

  15. Gansevoort RT, Arici M, Benzing T, Birn H, Capasso G, Covic A, et al. Recommendations for the use of tolvaptan in autosomal dominant polycystic kidney disease: a position statement on behalf of the ERA-EDTA working groups on inherited kidney disorders and European renal best practice. Nephrol Dial Transpl. 2016;31:337–48.

    Article  Google Scholar 

  16. Mustafa RA, Yu ASL. Burden of proof for Tolvaptan in ADPKD: did REPRISE provide the answer? Clin J Am Soc Nephrol. 2018;13:1107–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. Perrone RD, Abebe KZ, Watnick TJ, Althouse AD, Hallows KR, Lalama CM, et al. Primary results of the randomized trial of metformin administration in polycystic kidney disease (TAME PKD). Kidney Int. 2021;100:684–96.

    CAS  PubMed  Article  Google Scholar 

  18. Arroyo J, Escobar-Zarate D, Wells HH, Constans MM, Thao K, Smith JM, et al. The genetic background significantly impacts the severity of kidney cystic disease in the Pkd1RC/RC mouse model of autosomal dominant polycystic kidney disease. Kidney Int. 2021;99:1392–407.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. Wang J, Tripathy N, Chung EJ. Targeting and therapeutic peptide-based strategies for polycystic kidney disease. Adv Drug Deliv Rev. 2020;161-2:176–89.

    Article  CAS  Google Scholar 

  20. Seeger-Nukpezah T, Geynisman DM, Nikonova AS, Benzing T, Golemis EA. The hallmarks of cancer: relevance to the pathogenesis of polycystic kidney disease. Nat Rev Nephrol. 2015;11:515–34.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  21. Higgins M, Obaidi I, McMorrow T. Primary cilia and their role in cancer. Oncol Lett. 2019;17:3041–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Hildebrandt F, Benzing T, Katsanis N. Ciliopathies. N Engl J Med. 2011;364:1533–43.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  23. Wang S, Dong Z. Primary cilia and kidney injury: current research status and future perspectives. Am J Physiol Ren Physiol. 2013;305:F1085–98.

    CAS  Article  Google Scholar 

  24. Ma M, Tian X, Igarashi P, Somlo S. Loss of cilia suppresses cyst growth in genetic models of autosomal dominant polycystic kidney disease. Nat Genet. 2013;45:1004–12.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. Lehman JM, Michaud EJ, Schoeb TR, Aydin-Son Y, Miller M, Yoder BK. The Oak Ridge Polycystic Kidney mouse: modeling ciliopathies of mice and men. Dev Dyn. 2008;237:1960–71.

    PubMed  PubMed Central  Article  Google Scholar 

  26. Hopp K, Ward CJ, Hommerding CJ, Nasr SH, Tuan HF, Gainullin VG, et al. Functional polycystin-1 dosage governs autosomal dominant polycystic kidney disease severity. J Clin Invest. 2012;122:4257–73.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. Smith LA, Bukanov NO, Husson H, Russo RJ, Barry TC, Taylor AL, et al. Development of polycystic kidney disease in juvenile cystic kidney mice: insights into pathogenesis, ciliary abnormalities, and common features with human disease. J Am Soc Nephrol. 2006;17:2821–31.

    CAS  PubMed  Article  Google Scholar 

  28. Liu X, Vien T, Duan J, Sheu SH, Decaen PG, Clapham DE. Polycystin-2 is an essential ion channel subunit in the primary cilium of the renal collecting duct epithelium. Elife. 2018;7:e33183.

    PubMed  PubMed Central  Article  Google Scholar 

  29. Shao L, El-Jouni W, Kong F, Ramesh J, Kumar RS, Shen X, et al. Genetic reduction of cilium length by targeting intraflagellar transport 88 protein impedes kidney and liver cyst formation in mouse models of autosomal polycystic kidney disease. Kidney Int. 2020;98:1225–41.

    CAS  PubMed  Article  Google Scholar 

  30. Husson H, Moreno S, Smith LA, Smith MM, Russo RJ, Pitstick R, et al. Reduction of ciliary length through pharmacologic or genetic inhibition of CDK5 attenuates polycystic kidney disease in a model of nephronophthisis. Hum Mol Genet. 2016;25:2245–55.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. Yang B, Sonawane ND, Zhao D, Somlo S, Verkman AS. Small-molecule CFTR inhibitors slow cyst growth in polycystic kidney disease. J Am Soc Nephrol. 2008;19:1300–10.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. Shelanski ML, Gaskin F, Cantor CR. Microtubule assembly in the absence of added nucleotides. Proc Natl Acad Sci USA. 1973;70:765–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. Silva LM, Wang W, Allard BA, Pottorf TS, Jacobs DT, Tran PV. Analysis of primary cilia in renal tissue and cells. Methods Cell Biol. 2019;153:205–29.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. Calvet JP. The role of calcium and cyclic AMP in PKD. In: Li X, editor. Polycystic kidney disease. Chapter 8. Brisbane (AU): Codon Publications; 2015.

  35. Yoder BK. Role of primary cilia in the pathogenesis of polycystic kidney disease. J Am Soc Nephrol. 2007;18:1381–8.

    CAS  PubMed  Article  Google Scholar 

  36. Yuan S, Li J, Diener DR, Choma MA, Rosenbaum JL, Sun Z. Target-of-rapamycin complex 1 (Torc1) signaling modulates cilia size and function through protein synthesis regulation. Proc Natl Acad Sci USA. 2012;109:2021–6.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  37. Abdul-Majeed S, Moloney BC, Nauli SM. Mechanisms regulating cilia growth and cilia function in endothelial cells. Cell Mol Life Sci. 2012;69:165–73.

    CAS  PubMed  Article  Google Scholar 

  38. Sharma N, Bryant J, Wloga D, Donaldson R, Davis RC, Jerka-Dziadosz M, et al. Katanin regulates dynamics of microtubules and biogenesis of motile cilia. J Cell Biol. 2007;178:1065–79.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  39. Lee K, Battini L, Gusella GL. Cilium, centrosome and cell cycle regulation in polycystic kidney disease. Biochim Biophys Acta. 2011;1812:1263–71.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. Ishikawa H, Marshall WF. Intraflagellar transport and ciliary dynamics. Cold Spring Harb Perspect Biol. 2017;9:a021998.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  41. Follit JA, Tuft RA, Fogarty KE, Pazour GJ. The intraflagellar transport protein IFT20 is associated with the Golgi complex and is required for cilia assembly. Mol Biol Cell. 2006;17:3781–92.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  42. Lu H, Toh MT, Narasimhan V, Thamilselvam SK, Choksi SP, Roy S. A function for the Joubert syndrome protein Arl13b in ciliary membrane extension and ciliary length regulation. Dev Biol. 2015;397:225–36.

    CAS  PubMed  Article  Google Scholar 

  43. Larkins CE, Aviles GD, East MP, Kahn RA, Caspary T. Arl13b regulates ciliogenesis and the dynamic localization of Shh signaling proteins. Mol Biol Cell. 2011;22:4694–703.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  44. Berbari NF, Sharma N, Malarkey EB, Pieczynski JN, Boddu R, Gaertig J, et al. Microtubule modifications and stability are altered by cilia perturbation and in cystic kidney disease. Cytoskeleton. 2013;70:24–31.

    CAS  PubMed  Article  Google Scholar 

  45. Wheway G, Nazlamova L, Hancock JT. Signaling through the primary cilium. Front Cell Dev Biol. 2018;6:8.

    PubMed  PubMed Central  Article  Google Scholar 

  46. Tran PV, Talbott GC, Turbe-Doan A, Jacobs DT, Schonfeld MP, Silva LM, et al. Downregulating hedgehog signaling reduces renal cystogenic potential of mouse models. J Am Soc Nephrol. 2014;25:2201–12.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  47. Kyun ML, Kim SO, Lee HG, Hwang JA, Hwang J, Soung NK, et al. Wnt3a stimulation promotes primary ciliogenesis through β-catenin phosphorylation-induced reorganization of centriolar satellites. Cell Rep. 2020;30:1447–62.e5.

    CAS  PubMed  Article  Google Scholar 

  48. Lee EJ, Seo E, Kim JW, Nam SA, Lee JY, Jun J, et al. TAZ/Wnt-β-catenin/c-MYC axis regulates cystogenesis in polycystic kidney disease. Proc Natl Acad Sci USA. 2020;117:29001–12.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. Gao J, Zhou H, Lei T, Zhou L, Li W, Li X, et al. Curcumin inhibits renal cyst formation and enlargement in vitro by regulating intracellular signaling pathways. Eur J Pharmacol. 2011;654:92–9.

    CAS  PubMed  Article  Google Scholar 

  50. Su L, Liu L, Jia Y, Lei L, Liu J, Zhu S, et al. Ganoderma triterpenes retard renal cyst development by downregulating Ras/MAPK signaling and promoting cell differentiation. Kidney Int. 2017;92:1404–18.

    CAS  PubMed  Article  Google Scholar 

  51. He J, Zhou H, Meng J, Zhang S, Li X, Wang S, et al. Cardamonin retards progression of autosomal dominant polycystic kidney disease via inhibiting renal cyst growth and interstitial fibrosis. Pharmacol Res. 2020;155:104751.

    CAS  PubMed  Article  Google Scholar 

  52. Luesch H, Yoshida WY, Moore RE, Paul VJ, Mooberry SL. Isolation, structure determination, and biological activity of Lyngbyabellin A from the marine cyanobacterium lyngbya majuscula. J Nat Prod. 2000;63:611–5.

    CAS  PubMed  Article  Google Scholar 

  53. Nagle DG, Zhou YD, Park PU, Paul VJ, Rajbhandari I, Duncan CJ, et al. A new Indanone from the marine cyanobacterium Lyngbya majuscula that inhibits hypoxia-induced activation of the VEGF promoter in Hep3B cells. J Nat Prod. 2000;63:1431–3.

    CAS  PubMed  Article  Google Scholar 

  54. Patil SA, Patil R, Patil SA. Recent developments in biological activities of Indanones. Eur J Med Chem. 2017;138:182–98.

    CAS  PubMed  Article  Google Scholar 

  55. Delling M, DeCaen PG, Doerner JF, Febvay S, Clapham DE. Primary cilia are specialized calcium signalling organelles. Nature. 2013;504:311–4.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  56. Verghese E, Ricardo SD, Weidenfeld R, Zhuang J, Hill PA, Langham RG, et al. Renal primary cilia lengthen after acute tubular necrosis. J Am Soc Nephrol. 2009;20:2147–53.

    PubMed  PubMed Central  Article  Google Scholar 

  57. Verghese E, Weidenfeld R, Bertram JF, Ricardo SD, Deane JA. Renal cilia display length alterations following tubular injury and are present early in epithelial repair. Nephrol Dial Transpl. 2008;23:834–41.

    Article  Google Scholar 

  58. Han SJ, Jang HS, Kim JI, Lipschutz JH, Park KM. Unilateral nephrectomy elongates primary cilia in the remaining kidney via reactive oxygen species. Sci Rep. 2016;6:22281.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  59. Duong Phu M, Bross S, Burkhalter MD, Philipp M. Limitations and opportunities in the pharmacotherapy of ciliopathies. Pharmacol Ther. 2021;225:107841.

    CAS  PubMed  Article  Google Scholar 

  60. Li Y, Tian X, Ma M, Jerman S, Kong S, Somlo S, et al. Deletion of ADP ribosylation factor-like GTPase 13B leads to kidney cysts. J Am Soc Nephrol. 2016;27:3628–38.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  61. Lin F, Hiesberger T, Cordes K, Sinclair AM, Goldstein LS, Somlo S, et al. Kidney-specific inactivation of the KIF3A subunit of kinesin-II inhibits renal ciliogenesis and produces polycystic kidney disease. Proc Natl Acad Sci USA. 2003;100:5286–91.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  62. Besschetnova TY, Kolpakova-Hart E, Guan Y, Zhou J, Olsen BR, Shah JV. Identification of signaling pathways regulating primary cilium length and flow-mediated adaptation. Curr Biol. 2010;20:182–7.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  63. Rosengren T, Larsen LJ, Pedersen LB, Christensen ST, Møller LB. TSC1 and TSC2 regulate cilia length and canonical Hedgehog signaling via different mechanisms. Cell Mol Life Sci. 2018;75:2663–80.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  64. Jonassen JA, San Agustin J, Follit JA, Pazour GJ. Deletion of IFT20 in the mouse kidney causes misorientation of the mitotic spindle and cystic kidney disease. J Cell Biol. 2008;183:377–84.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  65. Plotnikova OV, Pugacheva EN, Golemis EA. Primary cilia and the cell cycle. Methods Cell Biol. 2009;94:137–60.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  66. Zhang C, Balbo B, Ma M, Zhao J, Tian X, Kluger Y, et al. Cyclin-dependent kinase 1 activity is a driver of cyst growth in polycystic kidney disease. J Am Soc Nephrol. 2021;32:41–51.

    CAS  PubMed  Article  Google Scholar 

  67. Zhang JQJ, Burgess J, Stepanova D, Saravanabavan S, Wong ATY, Kaldis P, et al. Role of cyclin-dependent kinase 2 in the progression of mouse juvenile cystic kidney disease. Lab Invest. 2020;100:696–711.

    CAS  PubMed  Article  Google Scholar 

  68. Li LX, Zhou JX, Wang X, Zhang H, Harris PC, Calvet JP, et al. Cross-talk between CDK4/6 and SMYD2 regulates gene transcription, tubulin methylation, and ciliogenesis. Sci Adv. 2020;6:eabb3154.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  69. Sharma N, Kosan ZA, Stallworth JE, Berbari NF, Yoder BK. Soluble levels of cytosolic tubulin regulate ciliary length control. Mol Biol Cell. 2011;22:806–16.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  70. Woo DD, Miao SY, Pelayo JC, Woolf AS. Taxol inhibits progression of congenital polycystic kidney disease. Nature. 1994;368:750–3.

    CAS  PubMed  Article  Google Scholar 

  71. Jaulin F, Kreitzer G. KIF17 stabilizes microtubules and contributes to epithelial morphogenesis by acting at MT plus ends with EB1 and APC. J Cell Biol. 2010;190:443–60.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  72. Ma M, Gallagher AR, Somlo S. Ciliary mechanisms of cyst formation in polycystic kidney disease. Cold Spring Harb Perspect Biol. 2017;9:a028209.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  73. Li A, Xu Y, Fan S, Meng J, Shen X, Xiao Q, et al. Canonical Wnt inhibitors ameliorate cystogenesis in a mouse ortholog of human ADPKD. JCI Insight. 2018;3:e95874.

    PubMed Central  Article  Google Scholar 

  74. Silva LM, Jacobs DT, Allard BA, Fields TA, Sharma M, Wallace DP, et al. Inhibition of Hedgehog signaling suppresses proliferation and microcyst formation of human Autosomal Dominant Polycystic Kidney Disease cells. Sci Rep. 2018;8:4985.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  75. Bangs F, Anderson KV. Primary cilia and mammalian Hedgehog signaling. Cold Spring Harb Perspect Biol. 2017;9:a028175.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  76. Anvarian Z, Mykytyn K, Mukhopadhyay S, Pedersen LB, Christensen ST. Cellular signalling by primary cilia in development, organ function and disease. Nat Rev Nephrol. 2019;15:199–219.

    PubMed  PubMed Central  Article  Google Scholar 

  77. Abdelhamed ZA, Wheway G, Szymanska K, Natarajan S, Toomes C, Inglehearn C, et al. Variable expressivity of ciliopathy neurological phenotypes that encompass Meckel-Gruber syndrome and Joubert syndrome is caused by complex de-regulated ciliogenesis, Shh and Wnt signalling defects. Hum Mol Genet. 2013;22:1358–72.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  78. Wheway G, Abdelhamed Z, Natarajan S, Toomes C, Inglehearn C, Johnson CA. Aberrant Wnt signalling and cellular over-proliferation in a novel mouse model of Meckel-Gruber syndrome. Dev Biol. 2013;377:55–66.

    CAS  PubMed  Article  Google Scholar 

Download references

Acknowledgements

We thank Dr. Peter Igarashi (University of Minnesota) and Dr. Stefan Somlo (Yale School of Medicine) for providing us with the Ksp-Cre and Pkd1flox/flox mice. This work was supported by the National Natural Science Foundation of China grants (81974083, 81873597 and 81800388).

Author information

Authors and Affiliations

Authors

Contributions

BXY and XWL designed the experiments. XWL performed the research and analyzed the data. XWL, HZ, JZH, ZWQ, SYW, SZ, YPA, AM, ML, YZQ, NNL, CQR and BXY interpreted the results. XWL and BXY drafted and edited the manuscript. JHR and MNW provided support for electron microscopy imaging techniques. All authors commented on and approved the final manuscript.

Corresponding author

Correspondence to Bao-xue Yang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Supplementary information

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Li, Xw., Ran, Jh., Zhou, H. et al. 1-Indanone retards cyst development in ADPKD mouse model by stabilizing tubulin and down-regulating anterograde transport of cilia. Acta Pharmacol Sin (2022). https://doi.org/10.1038/s41401-022-00937-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41401-022-00937-z

Keywords

  • ADPKD
  • primary cilia
  • Cysts
  • 1-Indanone
  • anterograde transport motor protein

Search

Quick links