An mTOR anti-sense oligonucleotide decreases polycystic kidney disease in mice with a targeted mutation in Pkd2

Human Molecular Genetics

Volumn 23, Issue 18, 2014, Pages 4919-4931

  Ravichandran, Kameswaran ^a   Zafar, Iram ^a   He, Zhibin ^a   Doctor, R Brian ^a   Moldovan, Radu ^a   Mullick, Adam E ^b   Edelstein, Charles L ^a  

^a UNIVERSITY OF COLORADO   (United States)

^b ISIS PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; CARRIER PROTEIN; POLYCYSTIC KIDNEY DISEASE 2 PROTEIN; POLYCYSTIN; RAPAMYCIN; RICTOR PROTEIN, MOUSE; TARGET OF RAPAMYCIN KINASE;

ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; CELL PROLIFERATION; DISEASE MODEL; DOG; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENE THERAPY; GENETICS; HUMAN; KIDNEY; KIDNEY POLYCYSTIC DISEASE; MDCK CELL LINE; METABOLISM; MOUSE; PATHOLOGY; PROCEDURES;

ANIMALS; CARRIER PROTEINS; CELL PROLIFERATION; DISEASE MODELS, ANIMAL; DOGS; GENE EXPRESSION REGULATION; GENETIC THERAPY; HUMANS; KIDNEY; MADIN DARBY CANINE KIDNEY CELLS; MICE; MICE, INBRED C57BL; OLIGONUCLEOTIDES, ANTISENSE; POLYCYSTIC KIDNEY DISEASES; SIROLIMUS; TOR SERINE-THREONINE KINASES; TRPP CATION CHANNELS;

EID: 84906840833     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddu208     Document Type: Article

References (57)

1. Grantham, J.J. (2008) Clinical practice. Autosomal dominant polycystic kidney disease. N. Engl. J. Med., 359, 1477-1485.
2. Wilson, P.D. (2004) Polycystic kidney disease. N. Engl. J. Med., 350, 151-164.
3. Trudel, M., D'Agati, V. and Costantini, F. (1991) C-myc as an inducer of polycystic kidney disease in transgenic mice. Kidney Int., 39, 665-671.
4. Schaffner, D.L., Barrios, R., Massey, C., Banez, E.I., Ou, C.N., Rajagopalan, S., Aguilar-Cordova, E., Lebovitz, R.M., Overbeek, P.A. and Lieberman, M.W. (1993) Targeting of the rasT24 oncogene to the proximal convoluted tubules in transgenic mice results in hyperplasia and polycystic kidneys. Am. J. Pathol., 142, 1051-1060.
5. Edelstein, C.L. (2008) Mammalian target of rapamycin and caspase inhibitors in polycystic kidney disease. Clin. J. Am. Soc. Nephrol., 3, 1219-1226.
6. Dazert, E. and Hall, M.N. (2011) mTOR signaling in disease. Curr. Opin. Cell Biol., 23, 744-755.
7. Loewith, R., Jacinto, E., Wullschleger, S., Lorberg, A., Crespo, J.L., Bonenfant, D., Oppliger, W., Jenoe, P. and Hall, M.N. (2002) Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol. Cell, 10, 457-468.
8. Wullschleger, S., Loewith, R. and Hall, M.N. (2006) TOR signaling in growth and metabolism. Cell, 124, 471-484.
9. Zoncu, R., Efeyan, A. and Sabatini, D.M. (2011) mTOR: from growth signal integration to cancer, diabetes and ageing. Nat. Rev. Mol. Cell. Biol., 12, 21-35.
10. Sarbassov, D.D., Ali, S.M., Kim, D.H., Guertin, D.A., Latek, R.R., Erdjument-Bromage, H., Tempst, P. and Sabatini, D.M. (2004) Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr. Biol., 14, 1296-1302.
11. Rodrik-Outmezguine, V.S., Chandarlapaty, S., Pagano, N.C., Poulikakos, P.I., Scaltriti, M., Moskatel, E., Baselga, J., Guichard, S. and Rosen, N. (2011) mTOR kinase inhibition causes feedback-dependent biphasic regulation of AKT signaling. Cancer Discov., 1, 248-259.
12. Sarbassov, D.D., Ali, S.M., Sengupta, S., Sheen, J.H., Hsu, P.P., Bagley, A.F., Markhard, A.L. and Sabatini, D.M. (2006) Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol. Cell, 22, 159-168.
13. Glidden, E.J., Gray, L.G., Vemuru, S., Li, D., Harris, T.E. and Mayo, M.W. (2012) Multiple site acetylation of Rictor stimulates mammalian target of rapamycin complex 2 (mTORC2)-dependent phosphorylation of Akt protein. J. Biol. Chem., 287, 581-588.
14. Shillingford, J.M., Murcia, N.S., Larson, C.H., Low, S.H., Hedgepeth, R., Brown, N., Flask, C.A., Novick, A.C., Goldfarb, D.A., Kramer-Zucker, A. et al. (2006) The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease. Proc. Natl. Acad. Sci. U.S.A., 103, 5466-5471.
15. Shillingford, J.M., Piontek, K.B., Germino, G.G. and Weimbs, T. (2010) Rapamycin ameliorates PKD resulting from conditional inactivation of Pkd1. J. Am. Soc. Nephrol., 21, 489-497.
16. Wahl, P.R., Serra, A.L., Le Hir, M., Molle, K.D., Hall, M.N. and Wuthrich, R.P. (2006) Inhibition ofmTORwith sirolimus slows disease progression in Han:SPRD rats with autosomal dominant polycystic kidney disease (ADPKD). Nephrol. Dial. Transplant., 21, 598-604.
17. Fischer, D.C., Jacoby, U., Pape, L., Ward, C.J., Kuwertz-Broeking, E., Renken, C., Nizze, H., Querfeld, U., Rudolph, B., Mueller-Wiefel, D.E. et al. (2009) Activation of the AKT/mTOR pathway in autosomal recessive polycystic kidney disease (ARPKD). Nephrol. Dial. Transplant., 24, 1819-1827.
18. Tao, Y., Kim, J., Schrier, R.W. and Edelstein, C.L. (2005) Rapamycin markedly slows disease progression in a rat model of polycystic kidney disease (PKD). J. Am. Soc. Nephrol., 16, 46-51.
19. Zafar, I., Belibi, F.A., He, Z. and Edelstein, C.L. (2009) Long-term rapamycin therapy in the Han:SPRD rat model of polycystic kidney disease (PKD). Nephrol. Dial. Transplant., 24, 2349-2353.
20. Shillingford, J.M., Leamon, C.P., Vlahov, I.R. and Weimbs, T. (2012) Folate-conjugated rapamycin slows progression of polycystic kidney disease. J. Am. Soc. Nephrol., 23, 1674-1681.
21. Zafar, I., Ravichandran, K., Belibi, F., Doctor, R.B. and Edelstein, C.L. (2010) Sirolimus attenuates disease progression in an orthologous mouse model of human autosomal dominant polycystic kidney disease. Kidney Int., 78, 754-761.
22. Belibi, F., Ravichandran, K., Zafar, I., He, Z. and Edelstein, C.L. (2011) mTORC1/2 and rapamycin in female Han:SPRD rats with polycystic kidney disease. Am. J. Physiol., 300, F236-F244.
23. Renken, C., Fischer, D.C., Kundt, G., Gretz, N. and Haffner, D. (2011) 'Inhibition of mTOR with sirolimus does not attenuate progression of liver and kidney disease in PCK rats. Nephrol. Dial. Transplant., 26, 92-100.
24. Walz, G., Budde, K., Mannaa, M., Nurnberger, J., Wanner, C., Sommerer, C., Kunzendorf, U., Banas, B., Horl, W.H., Obermuller, N. et al. (2010) Everolimus in patients with autosomal dominant polycystic kidney disease. N. Engl. J. Med., 363, 830-840.
25. Serra, A.L., Poster, D., Kistler, A.D., Krauer, F., Raina, S., Young, J., Rentsch, K.M., Spanaus, K.S., Senn, O., Kristanto, P. et al. (2010) Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. N. Engl. J. Med., 363, 820-829.
26. Natoli, T.A., Smith, L.A., Rogers, K.A., Wang, B., Komarnitsky, S., Budman, Y., Belenky, A., Bukanov, N.O., Dackowski, W.R., Husson, H. et al. (2010) Inhibition of glucosylceramide accumulation results in effective blockade of polycystic kidney disease in mouse models. Nat. Med., 16, 788-792.
27. Becker, J.U., Saez, A.O., Zerres, K., Witzke, O., Hoyer, P.F., Schmid, K.W., Kribben, A., Bergmann, C. and Nurnberger, J. (2010) Them TOR pathway is activated in human autosomal-recessive polycystic kidney disease. Kidney Blood Press. Res., 33, 129-138.
28. Qian, Q., Hui, D., King, B.F., Kumar, S., Dean, P.G., Cosio, F.G. and Torres, V.E. (2008) Sirolimus reduces polycystic liver volume in ADPKD patients. J. Am. Soc. Nephrol., 19, 631-638.
29. Perico, N., Antiga, L., Caroli, A., Ruggenenti, P., Fasolini, G., Cafaro, M., Ondei, P., Rubis, N., Diadei, O., Gherardi, G. et al. (2010) Sirolimus therapy to halt the progression of ADPKD. J. Am. Soc. Nephrol, 21, 1031-1040.
30. Shor, B., Gibbons, J.J., Abraham, R.T. and Yu, K. (2009) Targeting mTOR globally in cancer; thinking beyond rapamycin. Cell Cycle, 8, 3831-3837.
31. Edelstein, C.L. (2005) What is the role of tubular epithelial cell apoptosis in polycystic kidney disease (PKD)? Cell Cycle, 4, e141-e145.
32. Tao, Y., Kim, J., Faubel, S., Wu, J.C., Falk, S.A., Schrier, R.W. and Edelstein, C.L. (2005) Caspase inhibition reduces tubular apoptosis and proliferation and slows disease progression in polycystic kidney disease (PKD). Proc. Natl. Acad. Sci. U.S.A., 102, 6954-6959.
33. Tao, Y., Zafar, I., Kim, J., Schrier, R.W. and Edelstein, C.L. (2007) Deletion of the caspase-3 gene markedly prolongs survival in the cpk mouse model of polycystic kidney disease (PKD). J. Am. Soc. Nephrol., 19, 749-755.
34. Thoreen, C.C. and Sabatini, D.M. (2009) Rapamycin inhibits mTORC1, but not completely. Autophagy, 5, 725-726.
35. Feldman, M.E., Apsel, B., Uotila, A., Loewith, R., Knight, Z.A., Ruggero, D. and Shokat, K.M. (2009) Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol., 7, e38.
36. Liu, Q., Thoreen, C., Wang, J., Sabatini, D. and Gray, N.S. (2011) mTOR mediated anti-cancer drug discovery. Drug Discov. Today Ther. Strateg., 6, 47-55.
37. Kim, M., Datta, A., Brakeman, P., Yu, W. and Mostov, K.E. (2007) Polarity proteins PAR6 and aPKC regulate cell death through GSK-3beta in 3D epithelial morphogenesis. J. Cell Sci., 120(Pt 14), 2309-2317.
38. Walid, S., Eisen, R., Ratcliffe, D.R., Dai, K., Hussain, M.M. and Ojakian, G.K. (2008) The PI 3-kinase and mTOR signaling pathways are important modulators of epithelial tubule formation. J. Cell. Physiol., 216, 469-479.
39. Marrs, J.A. (2010) Branching morphogenesis: Rac signaling 'PIX' tubulogenesis. Focus on 'Pak1 regulates branching morphogenesis in 3D MDCK cell culture by a PIX and beta1-integrin-dependent mechanism'. Am. J. Physiol Cell Physiol., 299, C7-10.
40. Wallace, D.P. (2011) Cyclic AMP-mediated cyst expansion. Biochim. Biophys. Acta, 1812, 1291-1300.
41. Guertin, D.A., Stevens, D.M., Saitoh, M., Kinkel, S., Crosby, K., Sheen, J.H., Mullholland, D.J., Magnuson, M.A., Wu, H. and Sabatini, D.M. (2009) mTORcomplex 2 is required for the development of prostate cancer induced by PTEN loss in mice. Cancer Cell, 15, 148-159.
42. Oh, W.J. and Jacinto, E. (2011) mTOR complex 2 signaling and functions. Cell Cycle, 10, 2305-2316.
43. Lazorchak, A.S. and Su, B. (2011) Perspectives on the role of mTORC2 in B lymphocyte development, immunity and tumorigenesis. Protein Cell, 2, 523-530.
44. Pignataro, G., Capone, D., Polichetti, G., Vinciguerra, A., Gentile, A., Di Renzo, G. and Annunziato, L. (2011) Neuroprotective, immunosuppressant and antineoplastic properties of mTOR inhibitors: current and emerging therapeutic options. Curr. Opin. Pharmacol., 11, 378-394.
45. Sarbassov, D.D., Guertin, D.A., Ali, S.M. and Sabatini, D.M. (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science, 307, 1098-1101.
46. Ikenoue, T., Inoki, K., Yang, Q., Zhou, X. and Guan, K.L. (2008) Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling. EMBO J., 27, 1919-1931.
47. Foster, K.G. and Fingar, D.C. (2010) Mammalian target of rapamycin (mTOR): conducting the cellular signaling symphony. J. Biol. Chem., 285, 14071-7.
48. Wu, G., D'Agati, V., Cai, Y., Markowitz, G., Park, J.H., Reynolds, D.M., Maeda, Y., Le, T.C., Hou, H. Jr, Kucherlapati, R. et al. (1998) Somatic inactivation of Pkd2 results in polycystic kidney disease. Cell, 93, 177-188.
49. Amura, C.R., Brodsky, K.S., Groff, R., Gattone, V.H., Voelkel, N.F. and Doctor, R.B. (2007) VEGF receptor inhibition blocks liver cyst growth in pkd2(WS25/2) mice. Am. J. Physiol. Cell Physiol, 293, C419-C428.
50. Doctor, R.B., Serkova, N., Hasebroock, K., Zafar, I. and Edelstein, C.L. (2010) Distinct patterns of kidney and liver cyst growth in Pkd2WS25/2 mice. Nephrol. Dial. Transplant., 25, 3496-3504.
51. Torres, V.E., Wang, X., Qian, Q., Somlo, S., Harris, P.C. and Gattone, V.H. (2004) Effective treatment of an orthologous model of autosomal dominant polycystic kidney disease. Nat. Med., 10, 363-364.
52. Chang, M.Y., Parker, E., El, N.M., Haylor, J.L. and Ong, A.C. (2007) Endothelin B receptor blockade accelerates disease progression in a murine model of autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol., 18, 560-569.
53. Wang, X., Ye, H., Ward, C.J., Chu, J.Y., Masyuk, T.V., LaRusso, N.F., Harris, P.C., Chow, B.K. and Torres, V.E. (2012) Insignificant effect of secretin in rodent models of polycystic kidney and liver disease. Am. J. Physiol. Renal. Physiol., 303, F1089-F1098.
54. Cowley, B.D. Jr, Rupp, J.C., Muessel, M.J. and Gattone, V.H. 2. (1997) Gender and the effect of gonadal hormones on the progression of inherited polycystic kidney disease in rats. Am. J. Kidney Dis., 29, 265-272.
55. Gao, J., Zhou, H., Lei, T., Zhou, L., Li, W., Li, X. and Yang, B. (2011) Curcumin inhibits renal cyst formation and enlargement in vitro by regulating intracellular signaling pathways. Eur. J. Pharmacol., 654, 92-99.
56. Putnam, W.C., Swenson, S.M., Reif, G.A., Wallace, D.P., Helmkamp, G.M. Jr and Grantham, J.J. (2007) Identification of a forskolin-like molecule in human renal cysts. J. Am. Soc. Nephrol., 18, 934-943.
57. Dursun, B., He, Z., Somerset, H., Oh, D.J., Faubel, S. and Edelstein, C.L. (2006) Caspases and calpain are independent mediators of cisplatin-induced endothelial cell necrosis. Am. J. Physiol. Renal Physiol., 291, F578-F587.