Metabolic and phenotypic differences between mice producing a werner syndrome helicase mutant protein and WRN null mice

PLoS ONE

Volumn 10, Issue 10, 2015, Pages

  Aumailley, Lucie ^a   Garand, Chantal ^a   Dubois, Marie Julie ^b   Johnson, F Brad ^c   Marette, André ^b   Lebel, Michel ^a  

^a LAVAL UNIVERSITY   (Canada)

^b LAVAL UNIVERSITY   (Canada)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOKINE; DNA HELICASE; DRUG METABOLITE; HYDROXYPROLINE; INTERLEUKIN 10; INTERLEUKIN 18; LYSOPHOSPHATIDYLCHOLINE; PLASMINOGEN ACTIVATOR INHIBITOR 1; WERNER SYNDROME PROTEIN; REACTIVE OXYGEN METABOLITE; RECQ HELICASE; WERNER SYNDROME ATP DEPENDENT HELICASE; WRN PROTEIN, MOUSE;

AGING; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AUTOPHAGY; CARDIOVASCULAR RISK; CELL ORGANELLE; CONTROLLED STUDY; EMBRYO; ENDOPLASMIC RETICULUM; ENZYME LOCALIZATION; EXTRACELLULAR MATRIX; FEMALE; FIBROBLAST; INFLAMMATION; LIVER; MALE; METABOLOMICS; MOUSE; MUTANT; NONHUMAN; PEROXISOME; PHENOTYPE; PROTEIN ANALYSIS; RISK ASSESSMENT; WERNER SYNDROME; ANIMAL; BLOOD; C57BL MOUSE; CELL CULTURE; COMPARATIVE STUDY; ENZYMOLOGY; GENETICS; KNOCKOUT MOUSE; METABOLISM; MUTATION; OXIDATIVE STRESS; PROTEIN TRANSPORT;

ANIMALS; AUTOPHAGY; CELLS, CULTURED; ENDOPLASMIC RETICULUM; FEMALE; MALE; MICE, INBRED C57BL; MICE, KNOCKOUT; MUTATION; OXIDATIVE STRESS; PHENOTYPE; PROTEIN TRANSPORT; REACTIVE OXYGEN SPECIES; RECQ HELICASES; WERNER SYNDROME; WERNER SYNDROME HELICASE;

EID: 84945550655     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0140292     Document Type: Article

References (75)

1. Epstein CJ, Martin GM, Schultz AL, Motulsky AG. Werner's syndrome a review of its symptomatology, natural history, pathologic features, genetics and relationship to the natural aging process. Medicine (Baltimore). 1966;45(3):177-221. Epub 1966/05/01. PMID: 5327241.
2. Salk D. Werner's syndrome: a review of recent research with an analysis of connective tissue metabolism, growth control of cultured cells, and chromosomal aberrations. Hum Genet. 1982;62(1):1-5. Epub 1982/01/01. PMID: 6759366.
3. Yu CE, Oshima J, Fu YH, Wijsman EM, Hisama F, Alisch R, et al. Positional cloning of the Werner's syndrome gene. Science. 1996;272(5259):258-62. Epub 1996/04/12. PMID: 8602509.
4. Ozgenc A, Loeb LA. Current advances in unraveling the function of the Werner syndrome protein. Mutat Res. 2005;577(1-2):237-51. Epub 2005/06/11. S0027-5107 (05) 00185-5 [pii] doi: 10.1016/j. mrfmmm.2005.03.020 PMID: 15946710.
5. Kamath-Loeb AS, Shen JC, Loeb LA, Fry M. Werner syndrome protein. II. Characterization of the integral 3'->5' DNAexonuclease. J BiolChem. 1998;273(51):34145-50. Epub 1998/12/16. PMID: 9852074.
6. Huang S, Beresten S, Li B, Oshima J, Ellis NA, Campisi J. Characterization of the human and mouse WRN3'->5'exonuclease. Nucleic Acids Res. 2000;28(12):2396-405. Epub 2000/06/28. PMID: 10871373; PubMed Central PMCID: PMC102739.
7. Balajee AS, Machwe A, May A, Gray MD, Oshima J, Martin GM, et al. The Werner syndrome protein is involved in RNA polymerase II transcription. Mol Biol Cell. 1999;10(8):2655-68. Epub 1999/08/06. PMID: 10436020; PubMed Central PMCID: PMC25497.
8. Cooper MP, Machwe A, Orren DK, Brosh RM, Ramsden D, Bohr VA. Ku complex interacts with and stimulates the Werner protein. Genes Dev. 2000;14(8):907-12. Epub 2000/04/27. PMID: 10783163; PubMed Central PMCID: PMC316545.
9. Shen JC, Loeb LA. The Werner syndrome gene: the molecular basis of RecQ helicase-deficiency diseases. Trends Genet. 2000;16(5):213-20. Epub 2000/04/27. S0168-9525 (99) 01970-8 [pii]. PMID: 10782115.
10. Crabbe L, Verdun RE, Haggblom CI, Karlseder J. Defective telomere lagging strand synthesis in cells lacking WRN helicase activity. Science. 2004;306(5703):1951-3. Epub 2004/12/14. 306/5703/1951 [pii] doi: 10.1126/science.1103619 PMID: 15591207.
11. Saintigny Y, Makienko K, Swanson C, Emond MJ, Monnat RJ Jr. Homologous recombination resolution defect in werner syndrome. Mol Cell Biol. 2002;22(20):6971-8. Epub 2002/09/21. PMID: 12242278; PubMed Central PMCID: PMC139822.
12. Huang S, Lee L, Hanson NB, Lenaerts C, Hoehn H, Poot M, et al. The spectrum of WRN mutations in Werner syndrome patients. Human mutation. 2006;27(6):558-67. Epub 2006/05/05. doi: 10.1002/humu.20337 PMID: 16673358; PubMed Central PMCID: PMC1868417.
13. Friedrich K, Lee L, Leistritz DF, Nurnberg G, Saha B, Hisama FM, et al. WRN mutations in Werner syndrome patients: genomic rearrangements, unusual intronic mutations and ethnic-specific alterations. Hum Genet. 2010;128(1):103-11. Epub 2010/05/06. doi: 10.1007/s00439-010-0832-5 PMID: 20443122.
14. Lebel M, Leder P. A deletion within the murine Werner syndrome helicase induces sensitivity to inhibitors of topoisomerase and loss of cellular proliferative capacity. Proc Natl Acad Sci U S A. 1998;95(22):13097-102. Epub 1998/10/28. PMID: 9789047; PubMed Central PMCID: PMC23722.
15. Lebel M, Cardiff RD, Leder P. Tumorigenic effect of nonfunctional p53 or p21 in mice mutant in the Werner syndrome helicase. Cancer Res. 2001;61(5):1816-9. Epub 2001/03/31. PMID: 11280729.
16. Massip L, Garand C, Turaga RV, Deschenes F, Thorin E, Lebel M. Increased insulin, triglycerides, reactive oxygen species, and cardiac fibrosis in mice with a mutation in the helicase domain of the Werner syndrome gene homologue. Exp Gerontol. 2006;41(2):157-68. Epub 2005/12/07. S0531-5565 (05) 00259-7 [pii] doi: 10.1016/j.exger.2005.10.011 PMID: 16330174.
17. Lebel M, Lavoie J, Gaudreault I, Bronsard M, Drouin R. Genetic cooperation between the Werner syndrome protein and poly (ADP-ribose) polymerase-1 in preventing chromatid breaks, complex chromosomal rearrangements, and cancer in mice. Am J Pathol. 2003;162(5):1559-69. Epub 2003/04/23. S0002-9440 (10) 64290-3 [pii] doi: 10.1016/S0002-9440 (10) 64290-3 PMID: 12707040; PubMed Central PMCID: PMC1851180.
18. Massip L, Garand C, Paquet ER, Cogger VC, O'Reilly JN, Tworek L, et al. Vitamin C restores healthy aging in a mouse model for Werner syndrome. FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 2010;24(1):158-72. Epub 2009/09/11. doi: 10.1096/fj. 09-137133 PMID: 19741171.
19. Pagano G, Zatterale A, Degan P, d'Ischia M, Kelly FJ, Pallardo FV, et al. Multiple involvement of oxidative stress in Werner syndrome phenotype. Biogerontology. 2005;6(4):233-43. Epub 2005/12/08. doi: 10.1007/s10522-005-2624-1 PMID: 16333757.
20. Pagano G, Zatterale A, Degan P, d'Ischia M, Kelly FJ, Pallardo FV, et al. In vivo prooxidant state in Werner syndrome (WS): results from three WS patients and two WS heterozygotes. Free radical research. 2005;39(5):529-33. Epub 2005/07/23. doi: 10.1080/10715760500092683 PMID: 16036329.
21. Mori S, Yokote K, Morisaki N, Saito Y, Yoshida S. Inheritable abnormal lipoprotein metabolism in Werner's syndrome similar to familial hypercholesterolaemia. Eur J Clin Invest. 1990;20(2):137-42. Epub 1990/04/01. PMID: 2112477.
22. Le Couteur DG, Warren A, Cogger VC, Smedsrod B, Sorensen KK, De Cabo R, et al. Old age and the hepatic sinusoid. Anat Rec (Hoboken). 2008;291(6):672-83. Epub 2008/05/20. doi: 10.1002/ar.20661 PMID: 18484614.
23. Labbe A, Garand C, Cogger VC, Paquet ER, Desbiens M, Le Couteur DG, et al. Resveratrol improves insulin resistance hyperglycemia and hepatosteatosis but not hypertriglyceridemia, inflammation, and life span in a mouse model for Werner syndrome. The journals of gerontology Series A, Biological sciences and medical sciences. 2011;66(3):264-78. Epub 2010/10/27. doi: 10.1093/gerona/glq184 PMID: 20974729.
24. Trapeaux J, Busseuil D, Shi Y, Nobari S, Shustik D, Mecteau M, et al. Improvement of aortic valve stenosis by ApoA-I mimetic therapy is associated with decreased aortic root and valve remodeling in mice. British journal of pharmacology. 2013. Epub 2013/05/04. doi: 10.1111/bph.12236 PMID: 23638718.
25. Lombard DB, Beard C, Johnson B, Marciniak RA, Dausman J, Bronson R, et al. Mutations in the WRN gene in mice accelerate mortality in a p53-null background. Mol Cell Biol. 2000;20(9):3286-91. Epub 2000/04/11. PMID: 10757812; PubMed Central PMCID: PMC85622.
26. Moore G, Knoblaugh S, Gollahon K, Rabinovitch P, Ladiges W. Hyperinsulinemiaand insulin resistance in Wrn null mice fed a diabetogenic diet. Mech Ageing Dev. 2008;129(4):201-6. Epub 2008/02/26. S0047-6374 (07) 00196-0 [pii] doi: 10.1016/j.mad.2007.12.009 PMID: 18295300; PubMed Central PMCID: PMC2706000.
27. Illig T, Gieger C, Zhai G, Romisch-Margl W, Wang-Sattler R, Prehn C, et al. Agenome-wide perspective of genetic variation in human metabolism. Nature genetics. 2010;42(2):137-41. Epub 2009/12/29. doi: 10.1038/ng.507 PMID: 20037589.
28. Unterwurzacher I, Koal T, Bonn GK, Weinberger KM, Ramsay SL. Rapid sample preparation and simultaneous quantitation of prostaglandins and lipoxygenase derived fatty acid metabolites by liquid chromatography-mass spectrometry from small sample volumes. Clinical chemistry and laboratory medicine: CCLM/FESCC. 2008;46(11):1589-97. Epub2008/10/10. doi: 10.1515/CCLM.2008.323 PMID: 18842110.
29. Deschenes F, Massip L, Garand C, Lebel M. In vivo misregulation of genes involved in apoptosis, development and oxidative stress in mice lacking both functional Werner syndrome protein and poly (ADP-ribose) polymerase-1. Human molecular genetics. 2005;14(21):3293-308. Epub 2005/10/01. doi: 10.1093/hmg/ddi362 PMID: 16195394.
30. Harrison FE, Meredith ME, Dawes SM, Saskowski JL, May JM. Low ascorbic acid and increased oxidative stress in gulo (-/-) mice during development. Brain research. 2010;1349:143-52. Epub 2010/07/06. doi: 10.1016/j.brainres.2010.06.037 PMID: 20599829; PubMed Central PMCID: PMC2914834.
31. Lachapelle S, Gagne JP, Garand C, Desbiens M, Coulombe Y, Bohr VA, et al. Proteome-wideidentification of WRN-interacting proteins in untreated and nuclease-treated samples. Journal of proteome research. 2011;10(3):1216-27. Epub 2011/01/08. doi: 10.1021/pr100990s PMID: 21210717.
32. Manders EM, Stap J, Brakenhoff GJ, van Driel R, Aten JA. Dynamics of three-dimensional replication patterns during the S-phase, analysed by double labelling of DNA and confocal microscopy. Journal of cell science. 1992;103(Pt3):857-62. Epub 1992/11/01. PMID: 1478975.
33. Bolte S, Cordelieres FP. A guided tour into subcellular colocalization analysis in light microscopy. Journal of microscopy. 2006;224(Pt3):213-32. Epub 2007/01/11. doi: 10.1111/j.1365-2818.2006.01706.x PMID: 17210054.
34. Zito E, Hansen HG, Yeo GS, Fujii J, Ron D. Endoplasmic reticulum thiol oxidase deficiency leads to ascorbic acid depletion and noncanonical scurvy in mice. Molecular cell. 2012;48(1):39-51. Epub 2012/09/18. doi: 10.1016/j.molcel.2012.08.010 PMID: 22981861; PubMed Central PMCID: PMC3473360.
35. Ellman GL. Tissue sulfhydryl groups. Archives of biochemistry and biophysics. 1959;82(1):70-7. Epub 1959/05/01. PMID: 13650640.
36. Mizushima N, Yoshimori T. How to interpret LC3 immunoblotting. Autophagy. 2007;3(6):542-5. Epub 2007/07/06. PMID: 17611390.
37. Altunkaynak BZ, Ozbek E, Altunkaynak ME. Astereological and histological analysis of spleen on obese female rats, fed with high fat diet. Saudi medical journal. 2007;28(3):353-7. Epub 2007/03/06. PMID: 17334458.
38. Gotoh K, Inoue M, Masaki T, Chiba S, Shimasaki T, Ando H, et al. A novel anti-inflammatory role for spleen-derived interleukin-10 in obesity-induced inflammation in white adipose tissue and liver. Diabetes. 2012;61(8):1994-2003. Epub 2012/06/01. doi: 10.2337/db11-1688 PMID: 22648387; PubMed Central PMCID: PMC3402315.
39. Cook DN. The role of MIP-1 alpha in inflammation and hematopoiesis. Journal of leukocyte biology. 1996;59(1):61-6. Epub 1996/01/01. PMID: 8558069.
40. Guo Z, Tilburgs T, Wong B, Strominger JL. Dysfunction of dendritic cells in aged C57BL/6 mice leads to failure of natural killer cell activation and of tumor eradication. Proc Natl Acad Sci USA. 2014;111(39):14199-204. Epub 2014/09/17. doi: 10.1073/pnas.1414780111 PMID: 25225399; PubMed Central PMCID: PMC4191753.
41. Mc Kee AS, Pearce EJ. CD25+CD4+cells contribute to Th2 polarization during helminth infection by suppressing Th1 response development. J Immunol. 2004;173(2):1224-31. Epub 2004/07/09. PMID: 15240714.
42. Li L, Krajewski S, Reed JC, Choi YS. The apoptosis and proliferation of SAC-activated B cells by IL-10 are associated with changes in Bcl-2, Bcl-xL, and Mcl-1 expression. Cellular immunology. 1997;178(1):33-41. Epub 1997/05/25. doi: 10.1006/cimm.1997.1129 PMID: 9184696.
43. Gotoh K, Inoue M, Shiraishi K, Masaki T, Chiba S, Mitsutomi K, et al. Spleen-derived interleukin-10 downregulates the severity of high-fat diet-induced non-alcoholic fatty pancreas disease. PloS one. 2012;7(12):e53154. Epub 2013/01/04. doi: 10.1371/journal.pone.0053154 PMID: 23285260; PubMed Central PMCID: PMC3532347.
44. Gotoh K, Inoue M, Masaki T, Chiba S, Shiraishi K, Shimasaki T, et al. Obesity-related chronic kidney disease is associated with spleen-derived IL-10. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association-European Renal Association. 2013;28(5):1120-30. Epub 2012/12/12. doi: 10.1093/ndt/gfs440 PMID: 23229922.
45. Yang W, Yao Y, Yang YQ, Lu FT, Li L, Wang YH, et al. Differential modulation by IL-17A of Cholangitis versus Colitis in IL-2Ralpha deleted mice. PloS one. 2014;9(8):e105351. Epub 2014/08/19. doi: 10. 1371/journal.pone.0105351 PMID: 25133396; PubMed Central PMCID: PMC4136813.
46. Goto M, Sugimoto K, Hayashi S, Ogino T, Sugimoto M, Furuichi Y, et al. Aging-associated inflammation in healthy Japanese individuals and patients with Werner syndrome. Exp Gerontol. 2012;47(12):936-9. Epub 2012/09/11. doi: 10.1016/j.exger.2012.08.010 PMID: 22960593.
47. Iwaki T, Urano T, Umemura K. PAI-1, progress in understanding the clinical problem and its aetiology. British journal of haematology. 2012;157(3):291-8. Epub 2012/03/01. doi: 10.1111/j.1365-2141.2012. 09074.x PMID: 22360729.
48. Sadowski M, Zabczyk M, Undas A. Coronary thrombus composition: Links with inflammation, platelet and endothelial markers. Atherosclerosis. 2014;237(2):555-61. Epub 2014/12/03. doi: 10.1016/j. atherosclerosis.2014.10.020 PMID: 25463088.
49. Samad F, Ruf W. Inflammation, obesity, and thrombosis. Blood. 2013;122(20):3415-22. Epub 2013/10/05. doi: 10.1182/blood-2013-05-427708 PMID: 24092932; PubMed Central PMCID: PMC3829115.
50. Gils A, Declerck PJ. The structural basis forthe pathophysiological relevance of PAI-I in cardiovascular diseases and the development of potential PAI-I inhibitors. Thrombosis and haemostasis. 2004;91(3):425-37. Epub 2004/02/26. doi: 10.1160/TH03-12-0764 PMID: 14983217.
51. Lasic D, Bevanda M, Bosnjak N, Uglesic B, Glavina T, Franic T. Metabolic syndrome and inflammation markers in patients with schizophrenia and recurrent depressive disorder. Psychiatria Danubina. 2014;26(3):214-9. Epub 2014/09/06. PMID: 25191767.
52. Goldstein S, Moerman EJ, Fujii S, Sobel BE. Overexpression of plasminogen activator inhibitortype-1 in senescent fibroblasts from normal subjects and those with Werner syndrome. Journal of cellular physiology. 1994;161(3):571-9. Epub 1994/12/01. doi: 10.1002/jcp. 1041610321 PMID: 7962138.
53. Eren M, Boe AE, Klyachko EA, Vaughan DE. Role of plasminogen activator inhibitor-1 in senescence and aging. Seminars in thrombosis and hemostasis. 2014;40(6):645-51. Epub 2014/09/01. doi: 10. 1055/s-0034-1387883 PMID: 25173500.
54. Yamamoto K, Takeshita K, Saito H. Plasminogen activator inhibitor-1 in aging. Seminars in thrombosis and hemostasis. 2014;40(6):652-9. Epub 2014/08/15. doi: 10.1055/s-0034-1384635 PMID: 25122500.
55. West MD, Shay JW, Wright WE, Linskens MH. Altered expression of plasminogen activator and plasminogen activator inhibitor during cellular senescence. Exp Gerontol. 1996;31(1-2):175-93. Epub 1996/01/01. PMID: 8706787.
56. Mu XC, Higgins PJ. Differential growth state-dependent regulation of plasminogen activator inhibitor type-1 expression in senescent IMR-90 human diploid fibroblasts. Journal of cellular physiology. 1995;165(3):647-57. Epub 1995/12/01. doi: 10.1002/jcp. 1041650324 PMID: 7593245.
57. Brogren H, Wallmark K, Deinum J, Karlsson L, Jern S. Platelets retain high levels of active plasminogen activator inhibitor 1. PloS one. 2011;6(11):e26762. Epub 2011/11/10. doi: 10.1371/journal.pone. 0026762 PMID: 22069469; PubMed Central PMCID: PMC3206048.
58. Shao X, Li M, Luo C, Wang YY, Lu YY, Feng S, et al. Effects of rapamycin against paraquat-induced pulmonary fibrosis in mice. Journal of Zhejiang University Science B. 2015;16(1):52-61. Epub2015/01/07. doi: 10.1631/jzus. B1400229 PMID: 25559956; PubMed Central PMCID: PMC4288945.
59. Shkurupii VA, Kim LB, Potapova OV, Sharkova TV, Putyatina AN, Nikonova IK. Study of fibrotic complications and hydroxyproline content in mouse liver at different stages of generalized BCG-induced granulomatosis. Bulletin of experimental biology and medicine. 2014;157(4):466-9. Epub 2014/08/12. doi: 10.1007/s10517-014-2592-z PMID: 25110084.
60. Oguz S, Kanter M, Erboga M, Erenoglu C. Protective effects of thymoquinone against cholestatic oxidative stress and hepatic damage after biliary obstruction in rats. Journal of molecular histology. 2012;43(2):151-9. Epub 2012/01/25. doi: 10.1007/s10735-011-9390-y PMID: 22270828.
61. Imhasly S, Naegeli H, Baumann S, von Bergen M, Luch A, Jungnickel H, et al. Metabolomic biomarkers correlating with hepatic lipidosis in dairy cows. BMC veterinary research. 2014;10:122. Epub 2014/06/04. doi: 10.1186/1746-6148-10-122 PMID: 24888604; PubMed Central PMCID: PMC4048253.
62. Virmani A, Binienda Z. Role of carnitine esters in brain neuropathology. Molecular aspects of medicine. 2004;25(5-6):533-49. Epub 2004/09/15. doi: 10.1016/j.mam.2004.06.003 PMID: 15363640.
63. Stephens FB, Constantin-Teodosiu D, Greenhaff PL. New insights concerning the role of carnitine in the regulation of fuel metabolism in skeletal muscle. The Journal of physiology. 2007;581(Pt2):431-44. Epub 2007/03/03. doi: 10.1113/jphysiol.2006.125799 PMID: 17331998; PubMed Central PMCID: PMC2075186.
64. Hall D, Poussin C, Velagapudi VR, Empsen C, Joffraud M, Beckmann JS, et al. Peroxisomal and microsomal lipid pathways associated with resistance to hepatic steatosis and reduced pro-inflammatory state. J Biol Chem. 2010;285(40):31011-23. Epub 2010/07/09. doi: 10.1074/jbc. M110.127159 PMID: 20610391; PubMed Central PMCID: PMC2945592.
65. Wanders RJ. Metabolic functions of peroxisomes in health and disease. Biochimie. 2014;98:36-44. Epub 2013/09/10. doi: 10.1016/j.biochi.2013.08.022 PMID: 24012550.
66. Willett WC. Dietary fats and coronary heart disease. Journal of internal medicine. 2012;272(1):13-24. Epub 2012/05/16. doi: 10.1111/j.1365-2796.2012.02553.x PMID: 22583051.
67. Weijers RN. Lipid composition of cell membranes and its relevance in type 2 diabetes mellitus. Current diabetes reviews. 2012;8(5):390-400. Epub 2012/06/16. PMID: 22698081; PubMed Central PMCID: PMC3474953.
68. Titorenko VI, Rachubinski RA. Origin and spatiotemporal dynamics of the peroxisomal endomembrane system. Frontiers in physiology. 2014;5:493. Epub 2015/01/08. doi: 10.3389/fphys.2014.00493 PMID: 25566090; PubMed Central PMCID: PMC4267184.
69. Maity J, Bohr VA, Laskar A, Karmakar P. Transient overexpression of Werner protein rescues starvation induced autophagy in Werner syndrome cells. Biochimicaetbiophysicaacta. 2014;1842(12 Pt A):2387-94. Epub 2014/09/27. doi: 10.1016/j.bbadis.2014.09.007 PMID: 25257404.
70. Saha B, Cypro A, Martin GM, Oshima J. Rapamycin decreases DNA damage accumulation and enhances cell growth of WRN-deficient human fibroblasts. Aging cell. 2014;13(3):573-5. Epub 2013/12/07. doi: 10.1111/acel.12190 PMID: 24308646; PubMed Central PMCID: PMC4032596.
71. Talaei F, van Praag VM, Henning RH. Hydrogen sulfide restores a normal morphological phenotype in Werner syndrome fibroblasts, attenuates oxidative damage and modulates mTOR pathway. Pharmacological research: the official journal of the Italian Pharmacological Society. 2013;74:34-44. Epub 2013/05/25. doi: 10.1016/j.phrs.2013.04.011 PMID: 23702336.
72. He W, Wang B, Yang J, Zhuang Y, Wang L, Huang X, et al. Chloroquine improved carbon tetrachlorideinduced liver fibrosis through its inhibition of the activation of hepatic stellate cells: role of autophagy. Biological & pharmaceutical bulletin. 2014;37(9):1505-9. Epub 2014/09/02. PMID: 25177034.
73. Wang L, Ogburn CE, Ware CB, Ladiges WC, Youssoufian H, Martin GM, et al. Cellular Werner phenotypes in mice expressing a putative dominant-negative human WRN gene. Genetics. 2000;154(1):357-62. Epub 2000/01/11. PMID: 10628995; PubMed Central PMCID: PMC1460888.
74. Agrelo R, Sutz MA, Setien F, Aldunate F, Esteller M, Da Costa V, et al. A novel Werner Syndrome mutation: pharmacological treatment by read-through of nonsense mutations and epigenetic therapies. Epigenetics: official journal of the DNA Methylation Society. 2015;10(4):329-41. Epub 2015/04/02. doi: 10.1080/15592294.2015.1027853 PMID: 25830902.
75. Ishikawa Y, Sugano H, Matsumoto T, Furuichi Y, Miller RW, Goto M. Unusual features of thyroid carcinomas in Japanese patients with Werner syndrome and possible genotype-phenotype relations to cell type and race. Cancer. 1999;85(6):1345-52. Epub 1999/04/03. PMID: 10189141.