Inhibition of experimental liver cirrhosis in mice by telomerase gene delivery

Science

Volumn 287, Issue 5456, 2000, Pages 1253-1258

  Rudolph, Karl Lenhard ^a   Chang, Sandy ^a,b   Millard, Melissa ^a   Schreiber Agus, Nicole ^c   DePinho, Ronald A ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBON TETRACHLORIDE; RNA; TELOMERASE;

ADENOVIRUS; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL CYCLE; ENZYME ACTIVITY; GENE THERAPY; GENE TRANSFER; LIVER CIRRHOSIS; LIVER DISEASE; MOUSE; NONHUMAN; PRIORITY JOURNAL; TELOMERE; TRANSGENIC MOUSE;

ADENOVIRIDAE; ANIMALS; APOPTOSIS; CARBON TETRACHLORIDE; GENE THERAPY; GENE TRANSFER TECHNIQUES; GENETIC VECTORS; HEPATECTOMY; LIVER; LIVER CIRRHOSIS, EXPERIMENTAL; LIVER REGENERATION; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; MITOSIS; SPLEEN; TELOMERASE; TELOMERE; TRANSFORMING GROWTH FACTOR BETA;

EID: 0034681457     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.287.5456.1253     Document Type: Article

References (68)

1. R. G. Smart, R. E. Mann, H. J. Suurvali, J. Stud. Alcohol. 59, 245 (1998); R. G. Smart, R. E. Mann, S. L. Lee, Alcohol Alcohol. 31, 487 (1996); Morbid. Mortal. Wkly. Rep. 41, 969 (1993); R. G. Smart and R. E. Mann, J. Stud. Alcohol 52, 232 (1991); www.niddk. nih.gov/health/digest/pubs/cirrhosi/cirrhosi.htm.
2. R. G. Smart, R. E. Mann, H. J. Suurvali, J. Stud. Alcohol. 59, 245 (1998); R. G. Smart, R. E. Mann, S. L. Lee, Alcohol Alcohol. 31, 487 (1996); Morbid. Mortal. Wkly. Rep. 41, 969 (1993); R. G. Smart and R. E. Mann, J. Stud. Alcohol 52, 232 (1991); www.niddk. nih.gov/health/digest/pubs/cirrhosi/cirrhosi.htm.
3. R. G. Smart, R. E. Mann, H. J. Suurvali, J. Stud. Alcohol. 59, 245 (1998); R. G. Smart, R. E. Mann, S. L. Lee, Alcohol Alcohol. 31, 487 (1996); Morbid. Mortal. Wkly. Rep. 41, 969 (1993); R. G. Smart and R. E. Mann, J. Stud. Alcohol 52, 232 (1991); www.niddk. nih.gov/health/digest/pubs/cirrhosi/cirrhosi.htm.
4. R. G. Smart, R. E. Mann, H. J. Suurvali, J. Stud. Alcohol. 59, 245 (1998); R. G. Smart, R. E. Mann, S. L. Lee, Alcohol Alcohol. 31, 487 (1996); Morbid. Mortal. Wkly. Rep. 41, 969 (1993); R. G. Smart and R. E. Mann, J. Stud. Alcohol 52, 232 (1991); www.niddk. nih.gov/health/digest/pubs/cirrhosi/cirrhosi.htm.
5. S. L. Friedman, N. Engl. J. Med. 328, 1828 (1993); E. J. Williams and J. P. Iredale, Postgrad. Med. J. 870, 193 (1998); R. Alcolado, M. J. P. Arthur, J. P. Iredale, Clin. Sci. 92, 103 (1997).
6. S. L. Friedman, N. Engl. J. Med. 328, 1828 (1993); E. J. Williams and J. P. Iredale, Postgrad. Med. J. 870, 193 (1998); R. Alcolado, M. J. P. Arthur, J. P. Iredale, Clin. Sci. 92, 103 (1997).
7. S. L. Friedman, N. Engl. J. Med. 328, 1828 (1993); E. J. Williams and J. P. Iredale, Postgrad. Med. J. 870, 193 (1998); R. Alcolado, M. J. P. Arthur, J. P. Iredale, Clin. Sci. 92, 103 (1997).
8. M. Delhaye et al., Hepatology 23, 1003 (1996).
9. D. Roulot, A. M. Sevcsik, T. Coste, A. D. Strosberg, S. Marullo, Hepatology 29, 1730 (1999); N. Fausto, J. E. Mead, P. A. Gruppuso, A. Castilla, S. B. Jakowlew, Ciba Found. Symp. 157, 165 (1991); P. Bedossa, E. Peltier, B. Terris, D. Franco, T. Poynard, Hepatology 21, 760 (1995); S. Milani, H. Herbst, D. Schuppan, H. Stein, C. Surrenti, Am. J. Pathol. 139, 1221 (1991).
10. D. Roulot, A. M. Sevcsik, T. Coste, A. D. Strosberg, S. Marullo, Hepatology 29, 1730 (1999); N. Fausto, J. E. Mead, P. A. Gruppuso, A. Castilla, S. B. Jakowlew, Ciba Found. Symp. 157, 165 (1991); P. Bedossa, E. Peltier, B. Terris, D. Franco, T. Poynard, Hepatology 21, 760 (1995); S. Milani, H. Herbst, D. Schuppan, H. Stein, C. Surrenti, Am. J. Pathol. 139, 1221 (1991).
11. D. Roulot, A. M. Sevcsik, T. Coste, A. D. Strosberg, S. Marullo, Hepatology 29, 1730 (1999); N. Fausto, J. E. Mead, P. A. Gruppuso, A. Castilla, S. B. Jakowlew, Ciba Found. Symp. 157, 165 (1991); P. Bedossa, E. Peltier, B. Terris, D. Franco, T. Poynard, Hepatology 21, 760 (1995); S. Milani, H. Herbst, D. Schuppan, H. Stein, C. Surrenti, Am. J. Pathol. 139, 1221 (1991).
12. D. Roulot, A. M. Sevcsik, T. Coste, A. D. Strosberg, S. Marullo, Hepatology 29, 1730 (1999); N. Fausto, J. E. Mead, P. A. Gruppuso, A. Castilla, S. B. Jakowlew, Ciba Found. Symp. 157, 165 (1991); P. Bedossa, E. Peltier, B. Terris, D. Franco, T. Poynard, Hepatology 21, 760 (1995); S. Milani, H. Herbst, D. Schuppan, H. Stein, C. Surrenti, Am. J. Pathol. 139, 1221 (1991).
13. T. Kitada, S. Seki, N. Kawakita, T. Kuroki, T. Monna, Biochem. Biophys. Res. Commun. 211, 33 (1995); N. Miura et al., Cancer Genet. Cytogenet. 93, 56 (1997); Y. Urabe et al., Liver 16, 293 (1996).
14. T. Kitada, S. Seki, N. Kawakita, T. Kuroki, T. Monna, Biochem. Biophys. Res. Commun. 211, 33 (1995); N. Miura et al., Cancer Genet. Cytogenet. 93, 56 (1997); Y. Urabe et al., Liver 16, 293 (1996).
15. T. Kitada, S. Seki, N. Kawakita, T. Kuroki, T. Monna, Biochem. Biophys. Res. Commun. 211, 33 (1995); N. Miura et al., Cancer Genet. Cytogenet. 93, 56 (1997); Y. Urabe et al., Liver 16, 293 (1996).
16. A. G. Bodnar et al., Science 279, 349 (1998); H. Vaziri and S. Benchimol, Curr. Biol. 8, 279 (1998); C. M. Counter, Mutat. Res. 366, 45 (1996); T. Kiyono et al., Nature 396, 84 (1998).
17. A. G. Bodnar et al., Science 279, 349 (1998); H. Vaziri and S. Benchimol, Curr. Biol. 8, 279 (1998); C. M. Counter, Mutat. Res. 366, 45 (1996); T. Kiyono et al., Nature 396, 84 (1998).
18. A. G. Bodnar et al., Science 279, 349 (1998); H. Vaziri and S. Benchimol, Curr. Biol. 8, 279 (1998); C. M. Counter, Mutat. Res. 366, 45 (1996); T. Kiyono et al., Nature 396, 84 (1998).
19. A. G. Bodnar et al., Science 279, 349 (1998); H. Vaziri and S. Benchimol, Curr. Biol. 8, 279 (1998); C. M. Counter, Mutat. Res. 366, 45 (1996); T. Kiyono et al., Nature 396, 84 (1998).
20. M. A. Blasco et al., Cell 91, 25 (1997).
21. H. W. Lee et al., Nature 392, 569 (1998); K. L. Rudolph et al., Cell 96, 701 (1999).
22. H. W. Lee et al., Nature 392, 569 (1998); K. L. Rudolph et al., Cell 96, 701 (1999).
23. K. L. Rudolph, S. Chang, M. Millard, N. Schreiber-Agus, R. A. DePinho, unpublished data.
24. J. L. Heckel, E. P. Sandgren, J. L. Degen, R. D. Palmiter, R. L. Brinster, Cell 62, 447 (1990).
25. E. P. Sandgren et al., Cell 66, 245 (1991).
26. -/- mice.
27. N. Rufer, W. Dragowska, G. Thornbury, E. Roosnek, P. M. Lansdorp, Nature Biotechnol. 16, 743 (1998).
28. PH was performed as described (15). Briefly, mice were anesthetized by intraperitoneal (i.p.) injections of 2.5% Avertin. After ligation of the blood supply and resection of the left and the left-anterior lobes of the liver, the abdominal cavity was closed with peritoneal and dermal sutures. Regenerating livers were removed at the indicated time points, photographed with a Nikon 2000 camera, and fixed in 10% phosphate-buffered saline (PBS)-buffered formalin for histology.
29. K. L. Rudolph et al., Hepatology 30, 1159 (1999); A. M. Diehl and R. M. Rai, FASEB J. 10, 215 (1996).
30. K. L. Rudolph et al., Hepatology 30, 1159 (1999); A. M. Diehl and R. M. Rai, FASEB J. 10, 215 (1996).
31. Single-cell suspensions of regenerating livers were produced by homogenizing the organs between two glass slides. Homogenates were then filtered through a nylon mesh (60-μm opening; Sefor America, Kansas City, MO). After several washes with ice-cold PBS, single-cell suspensions were fixed in 70% ethanol and stained with propidium iodide.
32. B. McClintock, Genetics 26, 234 (1941); B. van Steensel, A. Smorgorzewska, T. de Lange, Cell 92, 401 (1998); E. Blackburn et al., Ciba Found. Symp. 211, 2 (1997); K. E. Kirk, B. P. Harmon, I. K. Reichardt, J. W. Sedat, E. H. Blackburn, Science 275, 1478 (1997).
33. B. McClintock, Genetics 26, 234 (1941); B. van Steensel, A. Smorgorzewska, T. de Lange, Cell 92, 401 (1998); E. Blackburn et al., Ciba Found. Symp. 211, 2 (1997); K. E. Kirk, B. P. Harmon, I. K. Reichardt, J. W. Sedat, E. H. Blackburn, Science 275, 1478 (1997).
34. B. McClintock, Genetics 26, 234 (1941); B. van Steensel, A. Smorgorzewska, T. de Lange, Cell 92, 401 (1998); E. Blackburn et al., Ciba Found. Symp. 211, 2 (1997); K. E. Kirk, B. P. Harmon, I. K. Reichardt, J. W. Sedat, E. H. Blackburn, Science 275, 1478 (1997).
35. B. McClintock, Genetics 26, 234 (1941); B. van Steensel, A. Smorgorzewska, T. de Lange, Cell 92, 401 (1998); E. Blackburn et al., Ciba Found. Symp. 211, 2 (1997); K. E. Kirk, B. P. Harmon, I. K. Reichardt, J. W. Sedat, E. H. Blackburn, Science 275, 1478 (1997).
36. R. P. Tamayo, Hepatology 3, 112 (1983).
37. K. R. Prowse and C. W. Greider, Proc. Natl. Acad. Sci. U.S.A. 92, 4818 (1995).
38. D. K. Podolsky and K. J. Isselbacher, in Harrison's Principles of Internal Medicine, A. S. Fauci et al., Eds. (McGraw-Hill, New York, ed. 14, 1998), p. 1704.
39. P. P. Anthony et al., Bull. WHO 55, 521 (1977).
40. 4. Formalin-fixed, paraffin-embedded liver sections were stained with Masson-trichrome, H&E, and reticulin.
41. A 5-kb Eco RI fragment of mTR including 4 kb of the upstream promoter region was cloned into the pAdTrack-Shuttle vector (24). Homologous recombination of Pme 1-linearized pAdTrack-mTR DNA with the viral backbone vector pAd-Easy-1 (24) was performed in Escherichia coli BJ5183 cells, yielding a replication-deficient (lack of E1/3) Ad5-mTR-virus. Virus was grown in 293 cells and purified as in (24).
42. T. C. He et al., Proc. Natl. Acad. Sci. U.S.A. 95, 2509 (1998).
43. 4 injections.
44. J. Korula, in N. Kaplowitz, Ed., Liver and Biliary Diseases (Williams & Wilkins, Baltimore, MD, 1992), pp. 529-541.
45. For immunostaining, 10-μm paraffin liver sections were incubated overnight at 4°C with 1:100 dilutions of the primary antibody (mouse anti-PCNA or mouse anti-TGF-β1) in the presence of 1.5% goat serum. The Elite Vectastain ABC kit (Vector Labs) was used for subsequent peroxidase substrate detection. Stained sections were dehydrated and mounted in Permount.
46. C. B. Harley, A. B. Futcher, C. W. Greider, Nature 345, 458 (1990); C. Mondello, R. Riboni, A. Casati, T. Nardo, F. Nuzzo, Exp. Cell Res. 236, 385 (1997); C. Pan, B. H. Xue, T. M. Ellis, D. J. Peace, M. O. Diaz, Exp. Cell Res. 231, 346 (1997); R. C. Allsopp and C. B. Harley, Exp. Cell Res. 219, 130 (1995).
47. C. B. Harley, A. B. Futcher, C. W. Greider, Nature 345, 458 (1990); C. Mondello, R. Riboni, A. Casati, T. Nardo, F. Nuzzo, Exp. Cell Res. 236, 385 (1997); C. Pan, B. H. Xue, T. M. Ellis, D. J. Peace, M. O. Diaz, Exp. Cell Res. 231, 346 (1997); R. C. Allsopp and C. B. Harley, Exp. Cell Res. 219, 130 (1995).
48. C. B. Harley, A. B. Futcher, C. W. Greider, Nature 345, 458 (1990); C. Mondello, R. Riboni, A. Casati, T. Nardo, F. Nuzzo, Exp. Cell Res. 236, 385 (1997); C. Pan, B. H. Xue, T. M. Ellis, D. J. Peace, M. O. Diaz, Exp. Cell Res. 231, 346 (1997); R. C. Allsopp and C. B. Harley, Exp. Cell Res. 219, 130 (1995).
49. C. B. Harley, A. B. Futcher, C. W. Greider, Nature 345, 458 (1990); C. Mondello, R. Riboni, A. Casati, T. Nardo, F. Nuzzo, Exp. Cell Res. 236, 385 (1997); C. Pan, B. H. Xue, T. M. Ellis, D. J. Peace, M. O. Diaz, Exp. Cell Res. 231, 346 (1997); R. C. Allsopp and C. B. Harley, Exp. Cell Res. 219, 130 (1995).
50. H. Niida et al. Nature Genet. 19, 203 (1998); L. Chin et al., Cell 97, 527 (1999).
51. H. Niida et al. Nature Genet. 19, 203 (1998); L. Chin et al., Cell 97, 527 (1999).
52. R. A. Greenberg et al., Cell 97, 515 (1999); W. C. Hahn et al., Nature 400, 464 (1999); J. W. Shay, J. Cell. Physiol. 173, 266 (1997); C. B. Harley et al., Cold Spring Harbor Symp. Quant. Biol. 59, 307 (1994); T. de Lange, Proc. Natl. Acad. Sci. U.S.A. 91, 2882 (1994).
53. R. A. Greenberg et al., Cell 97, 515 (1999); W. C. Hahn et al., Nature 400, 464 (1999); J. W. Shay, J. Cell. Physiol. 173, 266 (1997); C. B. Harley et al., Cold Spring Harbor Symp. Quant. Biol. 59, 307 (1994); T. de Lange, Proc. Natl. Acad. Sci. U.S.A. 91, 2882 (1994).
54. R. A. Greenberg et al., Cell 97, 515 (1999); W. C. Hahn et al., Nature 400, 464 (1999); J. W. Shay, J. Cell. Physiol. 173, 266 (1997); C. B. Harley et al., Cold Spring Harbor Symp. Quant. Biol. 59, 307 (1994); T. de Lange, Proc. Natl. Acad. Sci. U.S.A. 91, 2882 (1994).
55. R. A. Greenberg et al., Cell 97, 515 (1999); W. C. Hahn et al., Nature 400, 464 (1999); J. W. Shay, J. Cell. Physiol. 173, 266 (1997); C. B. Harley et al., Cold Spring Harbor Symp. Quant. Biol. 59, 307 (1994); T. de Lange, Proc. Natl. Acad. Sci. U.S.A. 91, 2882 (1994).
56. R. A. Greenberg et al., Cell 97, 515 (1999); W. C. Hahn et al., Nature 400, 464 (1999); J. W. Shay, J. Cell. Physiol. 173, 266 (1997); C. B. Harley et al., Cold Spring Harbor Symp. Quant. Biol. 59, 307 (1994); T. de Lange, Proc. Natl. Acad. Sci. U.S.A. 91, 2882 (1994).
57. H. Tahara et al., Cancer Res. 55, 2734 (1995); C. T. Huang et al., Eur. J. Cancer 34, 1946 (1998); Y. M. Park et al., Exp. Mol. Med. 30, 35 (1998); R. Nakishio, M. Kitamoto, T. Nakaishi, H. Takahashi, C. Kajiyama, Nippon Rinsho 56, 1239 (1998); T. Suda et al., Hepatology 27, 402 (1998); H. Kojima, O. Yokosuka, F. Imazeki, H. Saisho, M. Omata, Gastroenterology 112, 493 (1997).
58. H. Tahara et al., Cancer Res. 55, 2734 (1995); C. T. Huang et al., Eur. J. Cancer 34, 1946 (1998); Y. M. Park et al., Exp. Mol. Med. 30, 35 (1998); R. Nakishio, M. Kitamoto, T. Nakaishi, H. Takahashi, C. Kajiyama, Nippon Rinsho 56, 1239 (1998); T. Suda et al., Hepatology 27, 402 (1998); H. Kojima, O. Yokosuka, F. Imazeki, H. Saisho, M. Omata, Gastroenterology 112, 493 (1997).
59. H. Tahara et al., Cancer Res. 55, 2734 (1995); C. T. Huang et al., Eur. J. Cancer 34, 1946 (1998); Y. M. Park et al., Exp. Mol. Med. 30, 35 (1998); R. Nakishio, M. Kitamoto, T. Nakaishi, H. Takahashi, C. Kajiyama, Nippon Rinsho 56, 1239 (1998); T. Suda et al., Hepatology 27, 402 (1998); H. Kojima, O. Yokosuka, F. Imazeki, H. Saisho, M. Omata, Gastroenterology 112, 493 (1997).
60. H. Tahara et al., Cancer Res. 55, 2734 (1995); C. T. Huang et al., Eur. J. Cancer 34, 1946 (1998); Y. M. Park et al., Exp. Mol. Med. 30, 35 (1998); R. Nakishio, M. Kitamoto, T. Nakaishi, H. Takahashi, C. Kajiyama, Nippon Rinsho 56, 1239 (1998); T. Suda et al., Hepatology 27, 402 (1998); H. Kojima, O. Yokosuka, F. Imazeki, H. Saisho, M. Omata, Gastroenterology 112, 493 (1997).
61. H. Tahara et al., Cancer Res. 55, 2734 (1995); C. T. Huang et al., Eur. J. Cancer 34, 1946 (1998); Y. M. Park et al., Exp. Mol. Med. 30, 35 (1998); R. Nakishio, M. Kitamoto, T. Nakaishi, H. Takahashi, C. Kajiyama, Nippon Rinsho 56, 1239 (1998); T. Suda et al., Hepatology 27, 402 (1998); H. Kojima, O. Yokosuka, F. Imazeki, H. Saisho, M. Omata, Gastroenterology 112, 493 (1997).
62. H. Tahara et al., Cancer Res. 55, 2734 (1995); C. T. Huang et al., Eur. J. Cancer 34, 1946 (1998); Y. M. Park et al., Exp. Mol. Med. 30, 35 (1998); R. Nakishio, M. Kitamoto, T. Nakaishi, H. Takahashi, C. Kajiyama, Nippon Rinsho 56, 1239 (1998); T. Suda et al., Hepatology 27, 402 (1998); H. Kojima, O. Yokosuka, F. Imazeki, H. Saisho, M. Omata, Gastroenterology 112, 493 (1997).
63. J. P. Pommier et al., Virology 231, 148 (1997), W. S. Nichols, S. Schneider, R. C. Chan, C. F. Farthing, E. S. Daar, Scand. J. Immunol. 49, 302 (1999).
64. J. P. Pommier et al., Virology 231, 148 (1997), W. S. Nichols, S. Schneider, R. C. Chan, C. F. Farthing, E. S. Daar, Scand. J. Immunol. 49, 302 (1999).
65. J. H. Ohyashiki et al., Clin. Cancer Res. 5, 1155 (1999); 5. E. Ball et al., Blood 91, 3582 (1998); J. H. Ohyashiki et al., Cancer Res. 54, 3557 (1994).
66. J. H. Ohyashiki et al., Clin. Cancer Res. 5, 1155 (1999); S. E. Ball et al., Blood 91, 3582 (1998); J. H. Ohyashiki et al., Cancer Res. 54, 3557 (1994).
67. J. H. Ohyashiki et al., Clin. Cancer Res. 5, 1155 (1999); 5. E. Ball et al., Blood 91, 3582 (1998); J. H. Ohyashiki et al., Cancer Res. 54, 3557 (1994).
68. We thank I. Arias, G. Merlino, M. Meyerson, N. Sharpless, and C. David for critical reading of the manuscript; B. Vogelstein for the Ad-Easy-Adenovirus-System; J. Furgiueli for serum chemistry analysis; and V. V. Lam for technical assistance. Supported by Deutsche Forschungsgemeinschaft grant Ru 745/1-1 (K.L.R.), Leukemia Society of America fellowship (N.S.-A.), and the Dana-Farber Cancer Institute Cancer Core Grant (R.A.D.). R.A.D. is funded by NIH grants (R01HD34880 and R01HD28317), the American Heart Association Grant-in-Aid, and the American Cancer Society.