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Iaccarino, Daniele (2014) Expression and functional role of Ccdc80 in normal heart and cardiomyopathies. [Tesi di dottorato]

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Abstract (inglese)

Background: The gene Coiled Coil Domain Containing 80 (Ccdc80) is widely expressed in normal human tissues, at particularly high levels in heart, skeletal muscle and adipose tissue. Its role is well defined in tumor suppression, axon path finding, glucose homeostasis, bone marrow stromal cells and adipocyte differentiation. Moreover, it plays a role in embryonic development of lens and muscle, but no clear-cut data are available about the role of Ccdc80 in heart development and in heart disease.
Aims: To define if Ccdc80 is expressed during embryonic development of zebrafish heart and if its functional block causes alterations of heart structure or contractility; to define the expression pattern of Ccdc80 protein in normal heart vs cardiomyopathies in humans (samples taken from patients with dilated cardiomyopathy – DCM) and rodents (samples taken from right ventricle heart failure induced by monocrotaline – MCT).
Results: In zebrafish Ccdc80 is widely expressed in the forming heart, during all the developmental stages; Ccdc80-morphants show defects in the developing heart, with impaired cardiac looping, atrium enlargement, blood stasis and peripheral congestion. These phenotypical alterations, similar to heart failure, are due to a disorder of the late phase of cardiac development, after myocyte differentiation.
In normal human and rats, Ccdc80 mRNA, analized by Northern blot technique, showed a higher expression in atria compared to ventricles, while the Ccdc80 protein (108 Kd), analized by Western blot, showed similar expression levels in atria and ventricles. Ccdc80 protein showed different expression patterns, in atria and ventricles with a cytoplasmic localization and co-localization with sarcomeric proteins at immunofluorescence analysis.
In pathological samples (DCM and MCT rats) Ccd80 protein showed evident overexpression and different isoforms, related to protein phosphorylation and secreted protein isoform, suggesting a different feature in pathological conditions compared to normal.
Conclusions: Our results demonstrated that Ccdc80 has an indispensable role for correct heart development. In complete developed heart, Ccdc80 showed an adaptive function to stress conditions, such as pressure overload, and in cardiomyopathies showed increased expression and different isoforms

Abstract (italiano)

Introduzione: Il gene Coiled Coil Domain Containing 80 (Ccdc80) è ampiamente espresso in tessuti umani normali, a livelli particolarmente elevati nel cuore, muscolo scheletrico e tessuto adiposo. E’ ben definito il suo ruolo come oncosoppressore, nella innervazione degli assoni, nella omeostasi glicemica, e nel differenziamento delle cellule stromali del midollo osseo e degli adipociti. Inoltre, svolge un ruolo nello sviluppo embrionale muscolare e della lente del cristallino, ma non sono disponibili dati sul ruolo di Ccdc80 nello sviluppo del cuore e nelle malattie cardiache.
Obiettivi : Definire se Ccdc80 è espresso durante lo sviluppo embrionale del cuore zebrafish e se il suo blocco funzionale provoca alterazioni della struttura o della contrattilità; definire il pattern di espressione della proteina Ccdc80 nel cuore normale vs cardiomiopatie nell'uomo (campioni prelevati da pazienti con cardiomiopatia dilatativa - DCM ) e roditori (campioni prelevati da ratti con insufficienza ventricolare destra indotta da monocrotalina - MCT).
Risultati: In zebrafish Ccdc80 è ampiamente espresso nel cuore in formazione, durante tutte le fasi di sviluppo; i morfanti per Ccdc80 mostrano difetti nello sviluppo cardiaco, con alterato looping, dilatazione atriale, stasi ematica e congestione periferica. Queste alterazioni fenotipiche, simili ad uno scompenso cardiaco, sono dovuti ad un disturbo della fase tardiva dello sviluppo cardiaco, dopo che la differenziazione dei miociti è già stata completata.
Nei campioni normali di uomo e ratto, l’RNA messaggero di Ccdc80, analizzato con tecnica di Northern blot, è risultato maggiormente espresso negli atri rispetto ai ventricoli, il mentre l’espressione della proteina Ccdc80 (108 Kd), analizzata con tecnica Western blot, è risultata simile negli atri e nei ventricoli. La proteina Ccdc80 ha mostrato pattern di espressione diversi in atri e ventricoli, con localizzazione citoplasmatica e chiara co-localizzazione con le proteine sarcomeriche all’immunofluorescenza. Nei campioni patologici (DCM ed MCT ratti) la proteina Ccd80 ha mostrato una netta iper-espressione sia negli atri che nei ventricoli, e la presenza di diverse isoforme, suggerendo diverse funzioni in condizioni patologiche rispetto al normale .
Conclusioni: I nostri risultati hanno dimostrato che Ccdc80 ha un ruolo indispensabile nello sviluppo cardiaco. Nel cuore adulto, Ccdc80 si manifesta con diverse isoforme e maggiore espressione, rivestendo una funzione adattativa in condizioni di stress, come il sovraccarico di pressione, e nelle cardiomiopatie

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Tipo di EPrint:Tesi di dottorato
Relatore:Thiene, Gaetano
Correlatore:Angelini, Annalisa
Dottorato (corsi e scuole):Ciclo 25 > Scuole 25 > SCIENZE MEDICHE, CLINICHE E SPERIMENTALI > SCIENZE CARDIOVASCOLARI
Data di deposito della tesi:29 Gennaio 2014
Anno di Pubblicazione:29 Gennaio 2014
Parole chiave (italiano / inglese):Ccdc80, Cardiomyopathies
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/11 Malattie dell'apparato cardiovascolare
Area 06 - Scienze mediche > MED/08 Anatomia patologica
Struttura di riferimento:Dipartimenti > Dipartimento di Scienze Cardiologiche, Toraciche e Vascolari
Codice ID:6556
Depositato il:14 Nov 2014 12:29
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1. Maron BJ, Towbin JA, Thiene G. et al. Contemporary definitions and classification of the cardiomyopathies. An American Heart Association Scientific Statement from the Council on Clinical Cardiology,Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation. 2006; 113: 1807–1816. Cerca con Google

2. Elliott P, Andersson B, Arbustini E et al. Classification of the cardiomyopathies: a position statement from the european society of cardiology working group on myocardial and pericardial diseases. European Heart Journal. 2008; 29: 270–276. Cerca con Google

3. Taylor M R G, Carniel E, Mestroni L. Cardiomyopathy, familial dilated. Orphanet Journal of Rare Diseases. 2006; 1: 27. Cerca con Google

4. Towbin JA, Lowe AM, Colan SD et al. Incidence, causes, and outcomes of dilated cardiomyopathy in children. Journal of the American Medical Association. 2006; 296: 1867–1876. Cerca con Google

5. Towbin JA and Bowles NE. The failing heart. Nature. 2002; 415: 227–233. Cerca con Google

6. Richard P, Villard E, Charron P, Isnard R. The genetic bases of cardiomyopathies. Journal of the American College of Cardiology. 2006; 48: A79–A89. Cerca con Google

7. Hibbard JU, Lindheimer M, Lang RM. A modified definition for peripartum cardiomyopathy and prognosis based on echocardiography. Obstetrics and Gynecology. 1999; 94: 311–316. Cerca con Google

8. Johnson-Coyle L, Jensen L, Sobey A. Peripartum cardiomyopathy: review and practice guidelines. American Journal of Critical Care. 2012; 21: 89–99. Cerca con Google

9. Elkayam U, Akhter MW., Singh H et al. Pregnancy associated cardiomyopathy: clinical characteristics and a comparison between early and late presentation. Circulation. 2005; 111: 2050–2055. Cerca con Google

10. Sliwa K, Fett J, Elkayam U. Peripartum cardiomyopathy. Lancet. 2006; 368: 687–693. Cerca con Google

11. Ansari AA, Fett JD, Carraway RE, Mayne AE, Onlamoon N, Sundstrom JB. Autoimmune mechanisms as the basis for human peripartum cardiomyopathy. Clinical Cerca con Google

Reviews in Allergy and Immunology. 2002; 23: 301–324. Cerca con Google

12. Sliwa K, Forster O, Libhaber E et al. Peripartum cardiomyopathy: inflammatory markers as predictors of outcome in 100 prospectively studied patients. European HeartJournal. 2006; 27: 441–446. Cerca con Google

13. Torre-Amione G, Kapadia S, Benedict C, Oral H, Young JB, and Mann DL. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the studies of left ventricular dysfunction (SOLVD). Journal of the American College of Cardiology. 1996; 27: 1201–1206. Cerca con Google

14. Friedrich FW, Carrier L. Genetics of hypertrophic and dilated cardiomyopathy. Curr. Pharm. Biotechnol. 2012;13: 2467-76. Cerca con Google

15. Lobrinus JA, Janzer RC, Kuntzer T, Matthieu JM, Pfend G, Goy JJ, Bogousslavsky J. Familial cardiomyopathy and distal myopathy with abnormal desmin accumulation and migration. Neuromuscul. Disord. 1998; 8: 77–86. Cerca con Google

16. Ashrafian H, McKenna WJ, Watkins H. Disease pathways and novel therapeutic targets in hypertrophic cardiomyopathy. Circ. Res. 2011; 109: 86–96. Cerca con Google

17. Ho CY. Genetics and clinical destiny: improving care in hypertrophic cardiomyopathy. Circulation. 2010; 122: 2430–2440. Cerca con Google

18. Landstrom AP, Ackerman MJ. Mutation type is not clinically useful in predicting prognosis in hypertrophic cardiomyopathy. Circulation. 2010; 122: 2441–2449. Cerca con Google

19. Saffitz JE. Arrhythmogenic cardiomyopathy: advances in diagnosis and disease pathogenesis. Circulation. 2011; 124: e390–e392. Cerca con Google

20. Chien KR. Genotype, phenotype: upstairs, downstairs in the family of cardiomyopathies. J. Clin. Invest. 2003; 111: 175–178. Cerca con Google

21. Kamisago M, Sharma SD, DePalma SR, Solomon S, Sharma P, McDonough B, Smoot L, Mullen MP, Woolf PK, Wigle ED, Seidman JG, Seidman CE. Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy. N. Engl. J. Med. 2000; 343: 1688–1696. Cerca con Google

22. Dellefave L, McNally EM. The genetics of dilated cardiomyopathy. Curr. Opin. Cardiol. 2010; 25: 198–204. Cerca con Google

23. Villard E, Duboscq-Bidot L, Charron P, Benaiche A, Conraads V, Sylvius N, Komajda M. Mutation screening in dilated cardiomyopathy: prominent role of the beta myosin heavy chain gene. Eur. Heart J. 2005; 26: 794–803. Cerca con Google

24. Mogensen J, Murphy RT, Shaw T, Bahl A, Redwood C, Watkins H, Burke M, Elliott PM, McKenna WJ. Severe disease expression of cardiac troponin C and T mutations in patients with idiopathic dilated cardiomyopathy. J. Am. Coll. Cardiol. 2004; 44: 2033–2040. Cerca con Google

25. Hershberger RE, Siegfried JD. Update 2011: clinical and genetic issues in familial dilated cardiomyopathy. J. Am. Coll. Cardiol. 2011; 57: 1641–1649. Cerca con Google

26. Carballo S, Robinson P, Otway R, Fatkin D, Jongbloed JD, de Jonge N, Blair E, van Tintelen JP, Redwood C, Watkins H. Identification and functional characterization of cardiac troponin I as a novel disease gene in autosomal dominant dilated cardiomyopathy. Circ. Res. 2009; 105: 375–382. Cerca con Google

27. Murphy RT, Mogensen J, Shaw A, Kubo T, Hughes S, McKenna WJ. Novel mutation in cardiac troponin I in recessive idiopathic dilated cardiomyopathy. Lancet. 2004; 363: 371–372. Cerca con Google

28. Lakdawala NK, Dellefave L, Redwood CS, Sparks E, Cirino AL, Depalma S, Colan SD, Funke B, Zimmerman RS, Robinson P, Watkins H, Seidman CE, Seidman JG, McNally EM, Ho CY . Familial dilated cardiomyopathy caused by an alpha-tropomyosin mutation: the distinctive natural history of sarcomeric dilated cardiomyopathy. J. Am. Coll. Cardiol. 2010; 55: 320–329. Cerca con Google

29. Lakdawala NK, Givertz MM. Dilated cardiomyopathy with conduction disease and arrhythmia. Circulation. 2010; 122: 527–534. Cerca con Google

30. Olson TM, Kishimoto NY, Whitby FG, Michels VV. Mutations that alter the surface charge of alpha-tropomyosin are associated with dilated cardiomyopathy. J. Mol. Cell. Cardiol. 2001; 33: 723–732. Cerca con Google

31. Olson TM, Michels VV, Thibodeau SN, Tai YS, Keating MT. Actin mutations in dilated cardiomyopathy, a heritable form of heart failure. Science. 1998; 280: 750–752. Cerca con Google

32. Li D, Tapscoft T, Gonzalez O, Burch PE, Quiñones MA, Zoghbi WA, Hill R, Bachinski LL, Mann DL, Roberts R. Desmin mutation responsible for idiopathic dilated cardiomyopathy. Circulation. 1999; 100: 461–464. Cerca con Google

33. Goldfarb LG, Park KY, Cervenáková L, Gorokhova S, Lee HS, Vasconcelos Cerca con Google

O, Nagle JW, Semino-Mora C, Sivakumar K, Dalakas MC. Missense mutations in desmin associated with familial cardiac and skeletal myopathy. Nat. Genet. 1998; 19: 402–403. Cerca con Google

34. Muñoz-Mármol AM, Strasser G, Isamat M, Coulombe PA, Yang Y, Roca X, Vela E, Mate JL, Coll J, Fernández-Figueras MT, Navas- Palacios JJ, Ariza A, Fuchs E. A dysfunctional desmin mutation in a patient with severe generalized myopathy. Proc. Natl. Acad. Sci. U.S.A. 1998; 95: 11312–11317. Cerca con Google

35. Petrof BJ. Molecular pathophysiology of myofiber injury in deficiencies of the dystrophin–glycoprotein complex. Am. J. Phys. Med.Rehabil. 2002; 81: S162–S174. Cerca con Google

36. Monaco AP. Dystrophin, the protein product of the Duchenne/Becker muscular dystrophy gene. Trends Biochem. Sci. 1989; 14: 412–415. Cerca con Google

37. Muntoni F, Melis MA, Ganau A, Dubowitz V. Transcription of the dystrophin gene in normal tissues and in skeletal muscle of a family with X-linked dilated cardiomyopathy. Am. J. Hum. Genet. 1995; 56: 151–157. Cerca con Google

38. Minetti C, Bonilla E. Mosaic expression of dystrophin in carriers of Becker’s muscular dystrophy and the X-linked syndrome of myalgia and cramps. N. Engl. J. Med. 1992; 327: 1100. Cerca con Google

39. Tsubata S, Bowles KR, Vatta M, Zintz C, Titus J, Muhonen L, Bowles NE, Towbin JA. Mutations in the human delta-sarcoglycan gene in familial and sporadic dilated cardiomyopathy. J. Clin. Invest. 2000, 106: 655–662. Cerca con Google

40. Schmitt JP, Kamisago M, Asahi M, Li GH, Ahmad F, Mende U, Kranias EG, MacLennan DH, Seidman JG, Seidman CE. Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban. Science. 2003; 299: 1410–1413. Cerca con Google

41. Haghighi K, Kolokathis F, Gramolini AO, Waggoner JR, Pater L, Lynch RA, Fan GC, Tsiapras D, Parekh RR, Dorn GW 2nd, MacLennan DH, Kremastinos DT, Kranias EG. A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy. Proc. Natl. Acad. Sci. U.S.A. 2006; 103: 1388–1393. Cerca con Google

42. Charron P, Komajda M. Molecular genetics in hypertrophic cardiomyopathy: towards individualized management of the disease. Expert Review of Molecular Diagnostics, 2006; 6: 65–78. Cerca con Google

43. Elliott P, McKenna W.J. Hypertrophic cardiomyopathy. Lancet. 2004; 363: 1881–1891. Cerca con Google

44. Maron B J. Hypertrophic cardiomyopathy. Circulation. 2002; 106: 2419–2421. Cerca con Google

45. Richard P, Fressart V, Charron P, Hainque B. Genetics of inherited cardiomyopathies. Pathologie Biologie. 2010; 58: 343–352. Cerca con Google

46. Richard P, Villard E, Charron P, Isnard R. The genetic bases of cardiomyopathies. Journal of the American College of Cardiology. 2006; 48: A79–A89. Cerca con Google

47. Hershberger R E, Lindenfeld J, Mestroni L, Seidman C E, Taylor M R G, Towbin J A. Genetic evaluation of cardiomyopathy—a heart failure society of America practice guideline. Journal of Cardiac Failure. 2009; 15: 83–97. Cerca con Google

48. Xu Q, Dewey S, Nguyen S, Gomes A V. Malignant and benign mutations in familial cardiomyopathies: insights into mutations linked to complex cardiovascular phenotypes. Journal of Molecular and Cellular Cardiology. 2010;48: 899–909. Cerca con Google

49. Gimeno J R, Monserrat L, Perez-Sanchez I et al. Hypertrophic cardiomyopathy. A study of the troponin-T gene in 127 Spanish families. Revista Espanola de Cardiologia. 2009; 62: 1473–1477. Cerca con Google

50. Oakley C M. Report of the WHO/ISFC task force on the definition and classification of cardiomyopathies. British Heart Journal. 1980; 44: 672–673. Cerca con Google

51. Benotti J R, Grossman W, Cohn PF. Clinical profile of restrictive cardiomyopathy. Circulation. 1980; 61: 1206–1212. Cerca con Google

52. Rajagopalan N, Garcia M J, Rodriguez L et al. Comparison of new Doppler echocardiographic methods to differentiate constrictive pericardial heart disease and restrictive cardiomyopathy. American Journal of Cardiology. 2001; 87: 86–94. Cerca con Google

53. Kushwaha S S, Fallon J T, Fuster V. Medical progress—restrictive cardiomyopathy. New England Journal of Medicine. 1997; 336: 267–276. Cerca con Google

54. Fitzpatrick A P, Shapiro L M, Rickards A F, Poole-Wilson P A. Familial restrictive cardiomyopathy with atrioventricular block and skeletal myopathy”. British Heart Journal. 1990; 63 114–118. Cerca con Google

55. Thiene G, Corrado D, Basso C. Arrhythmogenic right ventricular cardiomyopathy/dysplasia. Orphanet Journal of Rare Diseases. 2007; 2: 45. Cerca con Google

56. McKenna W J et al. Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Task Force of the Working Group Myocardial and Pericardial Disease of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the International Society and Federation of Cardiology. British Heart Journal, 1994; 71: 215–218. Cerca con Google

57. Corrado D, Leoni L, Link M S et al. Implantable cardioverter-defibrillator therapy for prevention of sudden death in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia. Circulation. 2003; 108: 3084–3091. Cerca con Google

58. Nava A, Thiene G, Canciani B et al. Familial occurrence of right ventricular dysplasia: a study involving nine families. Journal of the American College of Cardiology. 1988, 12: 1222–1228. Cerca con Google

59. Rampazzo A, Nava A, Danieli G A et al. The gene for arrhythmogenic right ventricular cardiomyopathy maps to chromosome 14q23-q24. Human Molecular Genetics. 1994; 3: 959–962. Cerca con Google

60. Gerull B, Heuser A, Wichter T et al. Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. Nature Genetics. 2004; 36: 1162–1164. Cerca con Google

61. Bonn´e S, Van Hengel J, Van Roy F. Chromosomal mapping of human armadillo genes belonging to the p120(ctn)/plakophilin subfamily. Genomics. 1998; 51: 452–454. Cerca con Google

62. Syrris P, Ward D, Evans A et al. Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2. American Journal of Human Genetics. 2006; 79: 978–984. Cerca con Google

63. Pilichou K, Nava A, Basso C et al. Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy. Circulation. 2006; 113: 171–1179. Cerca con Google

64. Rampazzo A. Regulatory mutations in transforming growth factor-beta 3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1. Journal of the American College of Cardiology. 2005; 45: 10A–11A. Cerca con Google

65. Rampazzo A, Nava A, Malacrida S et al. Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular Cerca con Google

Cardiomyopathy. American Journal of Human Genetics. 2002; 71: 1200–1206. Cerca con Google

66. Tiso N, Stephan D A, Nava A et al. Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). HumanMolecular Genetics. 2001; 10: 189–194 Cerca con Google

67. Marcantonio D, Chalifour LE, Alaoui-Jamali MA, Alpert L, Huynh HT. Cloning and characterization of a novel gene that is regulated by estrogen and is associated with mammary gland carcinogenesis. Endocrinology. 2001; 142:2409–2418. Cerca con Google

68. Mu H, Ohta K, Kuriyama S, Shimada N, Tanihara H, Yasuda K, Tanaka H. Equarin, a novel soluble molecule expressed with polarity at chick embryonic lens equator, is involved in eye formation. Mech Dev. 2003; 120:143–155. Cerca con Google

69. Aoki K, Sun YJ, Aoki S, Wada K, Wada E. Cloning, expression, and mapping of a gene that is upregulated in adipose tissue of mice deficient in bombesin receptor subtype-3. Biochem Biophys Res Commun. 2002; 290:1282–1288. Cerca con Google

70. Bommer GT, Jager C, Durr EM, Baehs S, Eichhorst ST, Brabletz T, Hu G, Frohlich T, Arnold G, Kress DC, Goke B, Fearon ER, Kolligs FT. DRO1, a gene down-regulated by oncogenes, mediates growth inhibition in colon and pancreatic cancer cells. J Biol Chem. 2005; 280: 7962–7975. Cerca con Google

71. Visconti R, Schepis F, Iuliano R, Pierantoni GM, Zhang L, Carlomagno F, Battaglia C, Martelli ML, Trapasso F, Santoro M, Fusco A. Cloning and molecular characterization of a novel gene strongly induced by the adenovirus E1A gene in rat thyroid cells Oncogene. 2003; 22: 1087-97. Cerca con Google

72. Santoro M, Melillo RM, Grieco M, Berlingieri MT, Vecchio G and Fusco A. The TRK and RET tyrosine kinase oncogenes cooperate with ras in the neoplastic trasformation of a rat thyroid epithelial cell line. Cell Growth Differ. 1993; 4: 77-84. Cerca con Google

73. Pan J, Nakanishi K, Yutsudo M, Inoue H, Li Q, Oka K, Yoshioka N, Hakura A. Isolation of a novel gene down-regulated by v-src. FEBS Lett. 1996; 383: 21-25. Cerca con Google

74. Dry KL, Aldred MA, Edgar AJ, Brown J, Manson FD, Ho MF, Prosser J, Hardwick LJ, Lennon AA, Thomson K et al. Identification of a novel gene, ETX1 from Xp21.1, a candidate gene for X-linked retinitis pigmentosa (RP3). Hum Mol Genet. 1995; 4: 2347-53. Cerca con Google

75. Kurosawa H, Goi K, Inukai T, Inaba T, Cheng KS, Shinjyo T, Rakestraw KM, Naeve CW. Two candidate downstream target genes for E2A-HLF. Blood. 1999; 93: 321-32. Cerca con Google

76. Liu Y, Monticone M, Tonachini L, Mastrogiacomo M, Marigo V, Cancedda R, Castagnola P. URB expression in human bone marrow stromal cells and during mouse development. Biochem Biophys Res Commun. 2004; 322(2): 497-507. Cerca con Google

77. Pawłowski K, Muszewska A, Lenart A, Szczepińska T, Godzik A, Grynberg M. A widespread peroxiredoxin-like domain present in tumor suppression- and progression-implicated proteins. BMC Genomics. 2010; 11:590-608. Cerca con Google

78. Brusegan C, Pistocchi A, Frassine A, Della Noce I, Schepis F, et al. Ccdc80-l1 Is Involved in Axon Pathfinding of Zebrafish Motoneurons. PLoS ONE. 2012; 7(2): e31851. Cerca con Google

79. Lewis KE, Eisen JS. Hedgehog signaling is required for primary motoneuron induction in zebrafish. Development. 2001; 128: 3485–3495. Cerca con Google

80. Shimakage M, Kodama K, Kawahara K, Kim CJ, Ikeda Y, Yutsudo M, Inoue H: Cerca con Google

Downregulation of drs tumor suppressor gene in highly malignant human pulmonary neuroendocrine tumors. Oncol Rep. 2009; 21(6):1367-1372. Cerca con Google

81. Tambe Y, Yoshioka-Yamashita A, Mukaisho K, Haraguchi S, Chano T, Isono T, Cerca con Google

Kawai T, Suzuki Y, Kushima R, Hattori T, et al. Tumor prone phenotype of mice deficient in a novel apoptosis-inducing gene, drs. Carcinogenesis. 2007, 28(4):777-784. Cerca con Google

82. Tambe Y, Isono T, Haraguchi S, Yoshioka-Yamashita A, Yutsudo M, Inoue H. Cerca con Google

A novel apoptotic pathway induced by the drs tumor suppressor gene. Oncogene. 2004, 23(17):2977-2987. Cerca con Google

83. Tambe Y, Yamamoto A, Isono T, Chano T, Fukuda M, Inoue H. The drs tumor suppressor is involved in the maturation process of autophagy induced by low serum. Cancer Lett. 2009; 283(1):74-83. Cerca con Google

84. Manabe R, Tsutsui K, Yamada T, Kimura M, Nakano I, Shimono C, Sanzen N, Cerca con Google

Furutani Y, Fukuda T, Oguri Y, et al. Transcriptome-based systematic identification of extracellular matrix proteins. Proc Natl Acad Sci USA. 2008; 105(35):12849-12854. Cerca con Google

85. Ferraro A, Schepis F, Leone V, Federico A, Borbone E et al. Tumor Suppressor Role of the CL2/DRO1/CCDC80 Gene in Thyroid Carcinogenesis. J Clin Endocrinol Metab. 2013; 98: 2834–2843. Cerca con Google

86. Ferragud J, Avivar-Valderas A, Pla A, De Las Rivas J, de Mora JF. Transcriptional repression of the tumor suppressor DRO1 by AIB1. FEBS Lett. 2011; 585: 3041–3046. Cerca con Google

87. Anzick SL, Kononen J, Walker RL, Azorsa DO, Tanner MM, Guan XY, Cerca con Google

Sauter G, Kallioniemi OP, Trent JM, Meltzer PS. AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science. 1997; 277: 965–968. Cerca con Google

88. Ferrero M, Avivar A, Garcia-Macias MC, de Mora JF. Phosphoinositide 3-kinase/AKT signaling can promote AIB1 stabilityindependently of GSK3 phosphorylation. Cancer Res. 2008; 68: 5450–5459. Cerca con Google

88. Li H, Gomes PJ, Chen JD. RAC3, a steroid/nuclear receptor associated Cerca con Google

coactivator that is related to SRC-1 and TIF2. Proc. Natl. Acad. Sci. USA. 1997; 94: 8479–8484. Cerca con Google

89. Avivar A, Garcia-Macias MC, Ascaso E, Herrera G, O’Connor JE, de Mora, J.F. Moderate overexpression of AIB1 triggers pre-neoplastic changes in mammary epithelium. FEBS Lett. 2006; 580: 5222–5226. Cerca con Google

90. Okada T, Nishizawa H, Kurata A, Tamba S, Sonoda M, Yasui A, Kuroda Y, Hibuse T, Maeda N, Kihara S, Hadama T, Tobita K, et al. URB is abundantly expressed in adipose tissue and dysregulated in obesity. Biochemical and Biophysical Research Communications. 2008; 367: 370–376. Cerca con Google

91. Tremblay F, Revett T, Huard C, Zhang Y, Tobin J F, Martinez R V, Gimeno R E. Bidirectional Modulation of Adipogenesis by the Secreted Protein Ccdc80/DRO1/URB. The Journal of Biological Chemistery. 2009; 284: 8136–8147. Cerca con Google

92. Hu E, Liang P, Spiegelman B M. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J. Biol. Chem. 1996; 271: 10697–10703. Cerca con Google

93. MacDougald O A, Hwang C S, Fan H, Lane M D. Regulated expression of the obese gene product (leptin) in white adipose tissue and 3T3-L1 adipocytes. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 9034–9037. Cerca con Google

94. Kaestner K H, Christy R J, McLenithan J C, Braiterman L T, Cornelius P, Pekala P H, Lane M D. Sequence, tissue distribution, and differential expression of mRNA for a putative insulin-responsive glucose transporter in mouse 3T3-L1 adipocytes. Proc. Natl. Acad. Sci. U. S. A. 1989; 86, 3150–3154. Cerca con Google

95. Oishi Y, Manabe I, Tobe K, Tsushima K, Shindo T, Fujiu K, Nishimura G, Maemura K , Yamauchi T, Kubota N, Suzuki R, Kitamura T, Akira S, Kadowaki T, Nagai R. Krüppel-like transcription factor KLF5 is a key regulator of adipocyte differentiation Cell Metab. 2005; 1: 27–39. Cerca con Google

96. Tontonoz P, Hu E, Spiegelman B M.. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell. 1994; 79: 1147–1156. Cerca con Google

97. Longo K A, Wright W S, Kang S, Gerin I, Chiang S H, Lucas P C, Opp M R, MacDougald O A. Wnt10b inhibits development of white and brown adipose tissues. J. Biol. Chem. 2004; 279: 35503–35509. Cerca con Google

98. Tremblay F, Huard C, Jessie D, Gareski T, Will S, Richard A-M, Syed J, Bailey S, Brenneman K A, Martinez R V, Perreault M, Lin Q, Gimeno R E. Loss of Coiled-Coil Domain Containing 80 Negatively Modulates Glucose Homeostasis in Diet-Induced Cerca con Google

Obese Mice. Endocrinology. 2012; 153(9):4290–4303. Cerca con Google

99. O’Leary E E, Mazurkiewicz-Muñoz A M, Argetsinger L S, Maures T J, Huynh H T, Su C C. Identification of Steroid-Sensitive Gene-1/Ccdc80 as a JAK2-Binding Protein. Molecular Endocrinology 2013; 27:619-634. Cerca con Google

100. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005; 352:1779–1790. Cerca con Google

101. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005; 365:1054–1061. Cerca con Google

102. Aaronson DS, Horvath CM. A road map for those who know JAK-STAT. Science. 2002; 296: 1653–1655. Cerca con Google

103. Ohki-Hamazaki H, Watase K, Yamamoto K, et al. Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity. Nature. 1997; 390: 165–169. Cerca con Google

104. Raymond F, Métairon S, Kussmann M, Colomer J, Nascimento A, Mormeneo E, García-Martínez C, Gómez-Foix A M. Comparative gene expression profiling between human cultured myotubes and skeletal muscle tissue. BMC Genomics. 2010; 11: 125-141. Cerca con Google

105. Saenz A, Azpitarte M, Armananzas R, Leturcq F, Alzualde A, et al. Gene Expression Profiling in Limb-Girdle Muscular Dystrophy 2A. PLoS One. 2008; 3(11): e3750. Cerca con Google

106. Wang G, Surks H K, Mary Tang K, Zhu Y, Mendelsohn M E, Blanton R M. Steroid-sensitive Gene 1 Is a Novel Cyclic GMP-dependent Protein Kinase I Substrate in Vascular Smooth Muscle Cells. The Journal of biological Chemistry. 2013; 288: 24972–24983. Cerca con Google

107. Hofmann F, Ammendola A, Schlossmann J. Rising behind NO: cGMP-dependent protein kinases. J. Cell Sci. 2000; 113: 1671–1676. Cerca con Google

108. Blanton R M, Takimoto E, Lane A M, Aronovitz M, Piotrowski R, Karas R H, Kass D A, Mendelsohn M E. Protein kinase GI α inhibits pressure overload-induced cardiac remodeling and is required for the cardioprotective effect of sildenafil in vivo. J. Am. Heart Assoc. 2012; 1: e003731. Cerca con Google

109. Takimoto E, Champion H C, Li M, Belardi D, Ren S, Rodriguez E R, Bedja D, Gabrielson K L, Wang Y, Kass D A. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat. Med. 2005; 11: 214–222. Cerca con Google

110. Mirotsou M, Dzau V J, Pratt R E, Weinberg E O. Physiological genomics of cardiac disease. Quantitative relationships between gene expression and left ventricular hypertrophy. Physiol. Genomics. 2006; 27: 86–94. Cerca con Google

111. Vescovo G, Ceconi C, Bernocchi P, et al. Skeletal muscle myosin heavy chain expression in rats with monocrotaline-induced cardiac hypertrophy and failure. Relation to blood flow and degree of muscle atrophy. Cardiovasc Res. 1998; 39: 233-41. Cerca con Google

112. Angelini A, Castellani C, Ravara B, Franzin C, Pozzobon M, Tavano R, Dalla Libera L, Papini E, Vettor R, De Coppi P, Thiene G, Vescovo G. Stem-cell therapy in an experimental model of pulmonary hypertension and right heart failure: Role of paracrine and neurohormonal milieu in the remodeling process. The Journal of Heart and Lung Transplantation. 2011; 30: 1281-1293. Cerca con Google

113. Reindel J F, Rotht RA. The Effects of Monocrotaline Pyrrole on Cultured Bovine Pulmonary Artery Endothelial and Smooth Muscle Cells. American Journal of Pathology. 1991; 138: 707-719. Cerca con Google

114. Langleben D, Reid L M. Effect of methylprednisolone on monocrotaline-induced pulmonary vascular disease and right ventricular hypertrophy. Lab Invest. 1985; 52: 298-303. Cerca con Google

115. Hilliker K S, Garcia C M, Roth R A. Effects of monocrotaline and monocrotaline pyrrole on 5-hydroxytryptamine and paraquat uptake by lung slices. Res Commun Chem Pathol Pharmacol. 1983; 40: 179-197. Cerca con Google

116. Mattocks A R, White I N H. The conversion of pyrrolizidine alkaloids to N-oxides and to dihydropyrrolizidine derivatives by rat lung microsomes in vitro. Chem-Biol Interact. 1971; 3: 383-396. Cerca con Google

117. Barnes J M, Magee P N, Schoental R. Lesions in the lungs and livers of rats poisoned with the pyrrolizidine alkaloid fulvine and its N-oxide. J Pathol Bacteriol. 1964; 88: 521-531. Cerca con Google

118. Bruner L H, Hilliker K S, Roth R A. Pulmonary hypertension and ECG changes from monocrotaline pyrrole in the rat. Am J Physiol. 1983; 245: H300-H306. Cerca con Google

119. Kimmel C B, Ballard W W, Kimmel S R, Ullmann B, Schilling T F. Stages of embryonic development of the zebrafish. Dev Dyn, 1995; 203(3): 253-31. Cerca con Google

120. Patterson LJ, Gering M, Patient R. Scl is required for dorsal aorta as well as blood formation in zebrafish embryos. Blood. 2005; 105(9): 3502-11. Cerca con Google

121. Thiss C, Thiss B. High-resolution in situ hybridization to whole-mount zebrafish embryos. Nat Protoc. 2008; 3(1):59-69. Cerca con Google

122. Chen JN, Fishman MC. Zebrafish tinman homolog demarcates the heart field and initiates myocardial differentiation. Development. 1996; 122(12): 3809-16. Cerca con Google

123. Yelon D, Horne SA, Stainier DY. Restricted expression of cardiac myosin genes reveals regulated aspects of heart tube assembly in zebrafish. Dev Biol. 1999; 214: 23-37. Cerca con Google

124. Yutzey, KE, Rhee, JT, Bader, D. Expression of the atrialspecific myosin heavy chain AMHC1 and the establishment of anteroposterior polarity in the developing chicken heart. Development 1994; 120:871–883. Cerca con Google

125. Szeto DP, Griffin KJ, Kimelman D. HrT is required for cardiovascular development in zebrafish. Development. 2002; 129(21):5093-101. Cerca con Google

126. Stainier DY. Zebrafish genetics and vertebrate heart formation. Nat Rev Genet, 2001; 2(1): 39-48. Cerca con Google

127. Tirosh-Finkel1 L, Zeisel A, Brodt-Ivenshitz1 M, Shamai1 A, Yao1 Z, Seger1 R, Cerca con Google

Domany E, Tzahor1 E. BMP-mediated inhibition of FGF signaling promotes Cerca con Google

cardiomyocyte differentiation of anterior heart field progenitors. Development. 2010; 137: 2989-3000. Cerca con Google

128. Verhoeven M C, Haase C, Christoffels V M, Weidinger G, Bakkers J. Wnt Signaling Regulates Atrioventricular Canal Formation Upstream of BMP and Tbx2. Birth Defects Research. 2011; 91: 435-440. Cerca con Google

129. Klaus A, Saga Y, Taketo M M, Tzahor E, Birchmeier W. Distinct roles of Wnt/_-catenin and Bmp signalling during early cardiogenesis. PNAS. 2007; 104: 18531–18536. Cerca con Google

130. Westin J, Lardelli M. Three novel Notch genes in zebrafish: implications for vertebrate Notch gene evolution and function. Dev Genes Evol. 1997; 207(1): 51-63. Cerca con Google

131. Niessen K, Karsan A. Notch Signaling in Cardiac Development. Circ Res. 2008; 102: 1169-1181. Cerca con Google

132. Rossol-Allisona J, Stemmlea L N, Swenson-Fieldsd K I, Kellyb P,. Fieldsc P E, McCalla S J, Caseyb P J, Fieldsa T A. Rho GTPase activity modulates WNT3A/β-catenin signalling. Cell Signal. 2009; 21(11): 1559–1568. Cerca con Google

133. Galindo C L, Skinner M A, Errami M, Olson L D,Watson D A, Li J, McCormick J F, McIver L J, Kumar N M, Pham T Q, Garner H R. Transcriptional profile of isoproterenol-induced cardiomyopathy and comparison to exercise-induced cardiac hypertrophy and human cardiac failure. BMC Physiology 2009; 9: 23-45. Cerca con Google

134. Frantz S, Klaiber M, Baba H A, Oberwinkler H, Volker K, Gabner B, Bayer B, Abeber M, Schuh K,Feil R, Hofmann F, Kuhn M. Stress-dependent dilated cardiomyopathy in mice with cardiomyocyte-restricted inactivation of cyclic GMP-dependent protein kinase I European Heart Journal. 2013; 34: 1233–1244. Cerca con Google

135. Wang L, Pasha Z, Wang S, Li N, Feng Y, et al. Protein Kinase G1a Overexpression Increases Stem Cell Survival and Cardiac Function after Myocardial Infarction. PLoS ONE. 2013; 8(3): e60087. Cerca con Google

136. Xua Z, Leeb SR, Hanb J. Dual role of cyclic GMP in cardiac cell survival. The International Journal of Biochemistry & Cell Biology. 2013; 45: 1577– 1584. Cerca con Google

137. Ren Y, Young Lee M , Schliffke S, Paavola J, Amos P J, Ge X , Ye M , Zhu S, Senyei G, Lum L, Ehrlich B E, Qyang Y. Small molecule Wnt inhibitors enhance the efficiency of BMP-4-directed cardiac differentiation of human pluripotent stem cells. Journal of Molecular and Cellular Cardiology. 2011; 51: 280–287. Cerca con Google

138. M W Bergmann. WNT Signaling in Adult Cardiac Hypertrophy and Remodeling. Cerca con Google

Lessons Learned From Cardiac Development. Circulation Research 2010; 107:1198-1208. Cerca con Google

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