Pyrimethamine inhibits adult polycystic kidney disease by modulating STAT signaling pathways

Human Molecular Genetics

Volumn 20, Issue 21, 2011, Pages 4143-4154

  Takakura, Ayumi ^a   Nelson, Erik A ^b   Haque, Nadeem ^a   Humphreys, Benjamin D ^a   Zandi Nejad, Kambiz ^a   Frank, David A ^b   Zhou, Jing ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA TUBULIN; GLYCERALDEHYDE 3 PHOSPHATE DEHYDROGENASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; NSC 74859; POLYCYSTIN 1; PROTEIN INHIBITOR; PYRIMETHAMINE; S3I 201; STAT3 PROTEIN; STAT4 PROTEIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; AUTOSOMAL DOMINANT DISORDER; CELL PROLIFERATION; CONTROLLED STUDY; DRUG MECHANISM; GENE; GENE MUTATION; HUMAN; HUMAN CELL; KIDNEY FAILURE; KIDNEY ISCHEMIA; KIDNEY POLYCYSTIC DISEASE; MOUSE; NEWBORN; NONHUMAN; PKD1 GENE; PRIORITY JOURNAL; SIGNAL TRANSDUCTION;

ADULT; AMINOSALICYLIC ACIDS; ANIMALS; ANIMALS, NEWBORN; BENZENESULFONATES; CELL LINE; CYSTS; DISEASE MODELS, ANIMAL; GENE EXPRESSION; GENES, REPORTER; HUMANS; KIDNEY; MICE; MICE, KNOCKOUT; PHOSPHORYLATION; PHOSPHOTYROSINE; POLYCYSTIC KIDNEY, AUTOSOMAL DOMINANT; PYRIMETHAMINE; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR;

EID: 80053939641     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddr338     Document Type: Article

References (44)

1. Gabow, P.A. (1993) Autosomal dominant polycystic kidney disease. N. Engl. J. Med., 329, 332-342.
2. Peters, D.J. and Sandkuijl, L.A. (1992) Genetic heterogeneity of polycystic kidney disease in Europe. Contrib. Nephrol., 97, 128-139.
3. Takakura, A., Contrino, L., Beck, A.W. and Zhou, J. (2008) Pkd1 inactivation induced in adulthood produces focal cystic disease. J. Am. Soc. Nephrol., 19, 2351-2363.
4. Piontek, K., Menezes, L.F., Garcia-Gonzalez, M.A., Huso, D.L. and Germino, G.G. (2007) A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1. Nat. Med., 13, 1490-1495.
5. Lantinga-van Leeuwen, I.S., Leonhard, W.N., van der Wal, A., Breuning, M.H., de Heer, E. and Peters, D.J. (2007) Kidney-specific inactivation of the Pkd1 gene induces rapid cyst formation in developing kidneys and a slow onset of disease in adult mice. Hum. Mol. Genet., 16, 3188-3196.
6. Bonventre, J.V. (2003) Dedifferentiation and proliferation of surviving epithelial cells in acute renal failure. J. Am. Soc. Nephrol., 14 (Suppl. 1), S55-S61.
7. Takakura, A., Contrino, L., Zhou, X., Bonventre, J.V., Sun, Y., Humphreys, B.D. and Zhou, J. (2009) Renal injury is a third hit promoting rapid development of adult polycystic kidney disease. Hum. Mol. Genet., 18, 2523-2531.
8. Ghatpande, S., Goswami, S., Mascareno, E. and Siddiqui, M.A. (1999) Signal transduction and transcriptional adaptation in embryonic heart development and during myocardial hypertrophy. Mol. Cell. Biochem., 196, 93-97.
9. Mascareno, E., El-Shafei, M., Maulik, N., Sato, M., Guo, Y., Das, D.K. and Siddiqui, M.A. (2001) JAK/STAT signaling is associated with cardiac dysfunction during ischemia and reperfusion. Circulation, 104, 325-329.
10. Johansen, K.A., Iwaki, D.D. and Lengyel, J.A. (2003) Localized JAK/ STAT signaling is required for oriented cell rearrangement in a tubular epithelium. Development, 130, 135-145.
11. Pires-daSilva, A. and Sommer, R.J. (2003) The evolution of signalling pathways in animal development. Nat. Rev. Genet., 4, 39-49.
12. Xi, R., McGregor, J.R. and Harrison, D.A. (2003) A gradient of JAK pathway activity patterns the anterior-posterior axis of the follicular epithelium. Dev. Cell, 4, 167-177.
13. Aaronson, D.S. and Horvath, C.M. (2002) A road map for those who don't know JAK-STAT. Science, 296, 1653-1655.
14. Zhang, Y.W., Wang, L.M., Jove, R. and Vande Woude, G.F. (2002) Requirement of Stat3 signaling for HGF/SF-Met mediated tumorigenesis. Oncogene, 21, 217-226.
15. Grantham, J.J. (1997) Mechanisms of progression in autosomal dominant polycystic kidney disease. Kidney Int. Suppl., 63, S93-S97.
16. Merta, M., Tesar, V., Zima, T., Jirsa, M., Rysava, R. and Zabka, J. (1997) Inflammatory cytokine profile in autosomal dominant polycystic kidney disease. Contrib. Nephrol., 122, 35-37.
17. Qin, S., Taglienti, M., Nauli, S.M., Contrino, L., Takakura, A., Zhou, J. and Kreidberg, J.A. (2010) Failure to ubiquitinate c-Met leads to hyperactivation of mTOR signaling in a mouse model of autosomal dominant polycystic kidney disease. J. Clin. Invest., 120, 3617-3628.
18. Yokogami, K., Wakisaka, S., Avruch, J. and Reeves, S.A. (2000) Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR. Curr. Biol., 10, 47-50.
19. 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. USA, 103, 5466-5471.
20. Lieberthal, W., Fuhro, R., Andry, C.C., Rennke, H., Abernathy, V.E., Koh, J.S., Valeri, R. and Levine, J.S. (2001) Rapamycin impairs recovery from acute renal failure: role of cell-cycle arrest and apoptosis of tubular cells. Am. J. Physiol. Renal. Physiol., 281, F693-F706.
21. Masuda, M., Suzui, M., Yasumatu, R., Nakashima, T., Kuratomi, Y., Azuma, K., Tomita, K., Komiyama, S. and Weinstein, I.B. (2002) Constitutive activation of signal transducers and activators of transcription 3 correlates with cyclin D1 overexpression and may provide a novel prognostic marker in head and neck squamous cell carcinoma. Cancer Res., 62, 3351-3355.
22. Horiguchi, A., Oya, M., Shimada, T., Uchida, A., Marumo, K. and Murai, M. (2002) Activation of signal transducer and activator of transcription 3 in renal cell carcinoma: a study of incidence and its association with pathological features and clinical outcome. J. Urol., 168, 762-765.
23. Luan, F.L., Hojo, M., Maluccio, M., Yamaji, K. and Suthanthiran, M. (2002) Rapamycin blocks tumor progression: unlinking immunosuppression from antitumor efficacy. Transplantation, 73, 1565-1572.
24. Leonhard, W.N., van der Wal, A., Novalic, Z., Kunnen, S.J., Gansevoort, R.T., Breuning, M.H., de Heer, E. and Peters, D.J. (2011) Curcumin inhibits cystogenesis by simultaneous interference of multiple signaling pathways: in vivo evidence from a Pkd1-deletion model. Am. J. Physiol. Renal Physiol., 300, 1193-1202.
25. Kolpakova-Hart, E., Nicolae, C., Zhou, J. and Olsen, B.R. (2008) Col2-Cre recombinase is co-expressed with endogenous type II collagen in embryonic renal epithelium and drives development of polycystic kidney disease following inactivation of ciliary genes. Matrix Biol., 27, 505-512.
26. 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.
27. 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.
28. Canaud, G., Knebelmann, B., Harris, P.C., Vrtovsnik, F., Correas, J.M., Pallet, N., Heyer, C.M., Letavernier, E., Bienaime, F., Thervet, E. et al. (2010) Therapeutic mTOR inhibition in autosomal dominant polycystic kidney disease: what is the appropriate serum level? Am. J. Transplant., 10, 1701-1706.
29. Torres, V.E., Boletta, A., Chapman, A., Gattone, V., Pei, Y., Qian, Q., Wallace, D.P., Weimbs, T. and Wuthrich, R.P. (2010) Prospects for mTOR inhibitor use in patients with polycystic kidney disease and hamartomatous diseases. Clin. J. Am. Soc. Nephrol., 5, 1312-1329.
30. Nelson, E.A., Walker, S.R., Kepich, A., Gashin, L.B., Hideshima, T., Ikeda, H., Chauhan, D., Anderson, K.C. and Frank, D.A. (2008) Nifuroxazide inhibits survival of multiple myeloma cells by directly inhibiting STAT3. Blood, 112, 5095-5102.
31. Humphreys, B.D., Valerius, M.T., Kobayashi, A., Mugford, J.W., Soeung, S., Duffield, J.S., McMahon, A.P. and Bonventre, J.V. (2008) Intrinsic epithelial cells repair the kidney after injury. Cell Stem Cell, 2, 284-291.
32. Klinker, H., Langmann, P. and Richter, E. (1996) Plasma pyrimethamine concentrations during long-term treatment for cerebral toxoplasmosis in patients with AIDS. Antimicrob. Agents Chemother., 40, 1623-1627.
33. Giammarioli, A.M., Maselli, A., Casagrande, A., Gambardella, L., Gallina, A., Spada, M., Giovannetti, A., Proietti, E., Malorni, W. and Pierdominici, M. (2008) Pyrimethamine induces apoptosis of melanoma cells via a caspase and cathepsin double-edged mechanism. Cancer Res., 68, 5291-5300.
34. Siddiquee, K., Zhang, S., Guida, W.C., Blaskovich, M.A., Greedy, B., Lawrence, H.R., Yip, M.L., Jove, R., McLaughlin, M.M., Lawrence, N.J. et al. (2007) Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity. Proc. Natl Acad. Sci. USA, 104, 7391-7396.
35. Happe, H., Leonhard, W.N., van der Wal, A., van de Water, B., Lantinga-van Leeuwen, I.S., Breuning, M.H., de Heer, E. and Peters, D.J. (2009) Toxic tubular injury in kidneys from Pkd1-deletion mice accelerates cystogenesis accompanied by dysregulated planar cell polarity and canonical Wnt signaling pathways. Hum. Mol. Genet., 18, 2532-2542.
36. Oguariri, R.M., Adelsberger, J.W., Baseler, M.W. and Imamichi, T. (2010) Evaluation of the effect of pyrimethamine, an anti-malarial drug, on HIV-1 replication. Virus Res., 153, 269-276.
37. Fuke, H., Shiraki, K., Sugimoto, K., Tanaka, J., Beppu, T., Yoneda, K., Yamamoto, N., Ito, K., Masuya, M. and Takei, Y. (2007) Jak inhibitor induces S phase cell-cycle arrest and augments TRAIL-induced apoptosis in human hepatocellular carcinoma cells. Biochem. Biophys. Res. Commun., 363, 738-744.
38. Pang, M., Ma, L., Gong, R., Tolbert, E., Mao, H., Ponnusamy, M., Chin, Y.E., Yan, H., Dworkin, L.D. and Zhuang, S. (2010) A novel STAT3 inhibitor, S3I-201, attenuates renal interstitial fibroblast activation and interstitial fibrosis in obstructive nephropathy. Kidney Int., 78, 257-268.
39. Bhunia, A.K., Piontek, K., Boletta, A., Liu, L., Qian, F., Xu, P.N., Germino, F.J. and Germino, G.G. (2002) PKD1 induces p21(waf1) and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2. Cell, 109, 157-168.
40. Durbin, J.E., Hackenmiller, R., Simon, M.C. and Levy, D.E. (1996) Targeted disruption of the mouse Stat1 gene results in compromised innate immunity to viral disease. Cell, 84, 443-450.
41. Meraz, M.A., White, J.M., Sheehan, K.C., Bach, E.A., Rodig, S.J., Dighe, A.S., Kaplan, D.H., Riley, J.K., Greenlund, A.C., Campbell, D. et al. (1996) Targeted disruption of the Stat1 gene inmice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell, 84, 431-442.
42. Sahni, M., Ambrosetti, D.C., Mansukhani, A., Gertner, R., Levy, D. and Basilico, C. (1999) FGF signaling inhibits chondrocyte proliferation and regulates bone development through the STAT-1 pathway. Genes Dev., 13, 1361-1366.
43. Lu, W., Shen, X., Pavlova, A., Lakkis, M., Ward, C.J., Pritchard, L., Harris, P.C., Genest, D.R., Perez-Atayde, A.R. and Zhou, J. (2001) Comparison of Pkd1-targeted mutants reveals that loss of polycystin-1 causes cystogenesis and bone defects. Hum. Mol. Genet., 10, 2385-2396.
44. Nauli, S.M., Rossetti, S., Kolb, R.J., Alenghat, F.J., Consugar, M.B., Harris, P.C., Ingber, D.E., Loghman-Adham, M. and Zhou, J. (2006) Loss of polycystin-1 in human cyst-lining epithelia leads to ciliary dysfunction. J. Am. Soc. Nephrol., 17, 1015-1025.