Knockdown of plakophilin 2 downregulates MIR-184 through CpG hypermethylation and suppression of the E2F1 pathway and leads to enhanced adipogenesis in vitro

Circulation Research

Volumn 119, Issue 6, 2016, Pages 731-750

  Gurha, Priyatansh ^a   Chen, Xiaofan ^a   Lombardi, Raffaella ^a   Willerson, James T ^a   Marian, Ali J ^a  

^a UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

Author keywords

cardiomyopathy; DNA methylation; epigenetics; gene expression; heart failure; microRNA

Indexed keywords

CELL MARKER; CYCLIN D1; DECITABINE; DNA METHYLTRANSFERASE 1; HIPPO PROTEIN; MESSENGER RNA; MICRORNA; MICRORNA 184; PLAKOPHILIN; PLAKOPHILIN 2; RETINOBLASTOMA 1 PROTEIN; TRANSCRIPTION FACTOR E2F1; TRANSCRIPTION FACTOR NKX2.5; UNCLASSIFIED DRUG; WNT PROTEIN; E2F1 PROTEIN, MOUSE; MIRN184 MICRORNA, MOUSE;

ADIPOGENESIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARRHYTHMOGENESIS; ARTICLE; CARDIAC MUSCLE CELL; CARDIOMYOPATHY; CELL DEATH; CELL DIFFERENTIATION; CELL MATURATION; CELL PROLIFERATION; CONTROLLED STUDY; CPG ISLAND; DNA METHYLATION; DOWN REGULATION; GENE SILENCING; GENE TARGETING; IN VITRO STUDY; INTRACELLULAR SIGNALING; MESENCHYMAL STEM CELL; MICROFLUIDIC ANALYSIS; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; TRANSCRIPTION REGULATION; WNT SIGNALING PATHWAY; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL CULTURE; DEFICIENCY; GENETICS; KNOCKOUT MOUSE; METABOLISM; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ADIPOGENESIS; ANIMALS; CELLS, CULTURED; CPG ISLANDS; DNA METHYLATION; DOWN-REGULATION; E2F1 TRANSCRIPTION FACTOR; MICE; MICE, KNOCKOUT; MICRORNAS; MYOCYTES, CARDIAC; PLAKOPHILINS; SIGNAL TRANSDUCTION;

EID: 84980319998     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.116.308422     Document Type: Article

References (55)

1. Delmar M, McKenna WJ, The cardiac desmosome and arrhythmogenic cardiomyopathies: from gene to disease. Circ Res 2010 107 700 714. doi: 10.1161/CIRCRESAHA.110.223412
2. Lombardi R, Marian AJ, Molecular genetics and pathogenesis of arrhythmogenic right ventricular cardiomyopathy: a disease of cardiac stem cells. Pediatr Cardiol 2011 32 360 365. doi: 10.1007/s00246-011-9890-2
3. Basso C, Thiene G, Corrado D, Angelini A, Nava A, Valente M, Arrhythmogenic right ventricular cardiomyopathy. Dysplasia, dystrophy, or myocarditis? Circulation 1996 94 983 991
4. Corrado D, Basso C, Thiene G, McKenna WJ, Davies MJ, Fontaliran F, Nava A, Silvestri F, Blomstrom-Lundqvist C, Wlodarska EK, Fontaine G, Camerini F, Spectrum of clinicopathologic manifestations of arrhythmogenic right ventricular cardiomyopathy/dysplasia: a multicenter study. J Am Coll Cardiol 1997 30 1512 1520
5. McKoy G, Protonotarios N, Crosby A, Tsatsopoulou A, Anastasakis A, Coonar A, Norman M, Baboonian C, Jeffery S, McKenna WJ, Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet 2000 355 2119 2124. doi: 10.1016/S0140-6736(00)02379-5
6. Rampazzo A, Nava A, Malacrida S, Beffagna G, Bauce B, Rossi V, Zimbello R, Simionati B, Basso C, Thiene G, Towbin JA, Danieli GA, Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet 2002 71 1200 1206. doi: 10.1086/344208
7. den Haan AD, Tan BY, Zikusoka MN, Lladó LI, Jain R, Daly A, Tichnell C, James C, Amat-Alarcon N, Abraham T, Russell SD, Bluemke DA, Calkins H, Dalal D, Judge DP, Comprehensive desmosome mutation analysis in north americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Cardiovasc Genet 2009 2 428 435. doi: 10.1161/CIRCGENETICS.109.858217
8. Heuser A, Plovie ER, Ellinor PT, Grossmann KS, Shin JT, Wichter T, Basson CT, Lerman BB, Sasse-Klaassen S, Thierfelder L, MacRae CA, Gerull B, Mutant desmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet 2006 79 1081 1088. doi: 10.1086/509044
9. Syrris P, Ward D, Evans A, Asimaki A, Gandjbakhch E, Sen-Chowdhry S, McKenna WJ, Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2. Am J Hum Genet 2006 79 978 984. doi: 10.1086/509122
10. Li J, Radice GL, A new perspective on intercalated disc organization: implications for heart disease. Dermatol Res Pract 2010 2010 207835. doi: 10.1155/2010/207835
11. Quarta G, Syrris P, Ashworth M, Jenkins S, Zuborne Alapi K, Morgan J, Muir A, Pantazis A, McKenna WJ, Elliott PM, Mutations in the Lamin A/C gene mimic arrhythmogenic right ventricular cardiomyopathy. Eur Heart J 2012 33 1128 1136. doi: 10.1093/eurheartj/ehr451
12. Merner ND, Hodgkinson KA, Haywood AF, Connors S, French VM, Drenckhahn JD, Kupprion C, Ramadanova K, Thierfelder L, McKenna W, Gallagher B, Morris-Larkin L, Bassett AS, Parfrey PS, Young TL, Arrhythmogenic right ventricular cardiomyopathy type 5 is a fully penetrant, lethal arrhythmic disorder caused by a missense mutation in the TMEM43 gene. Am J Hum Genet 2008 82 809 821. doi: 10.1016/j.ajhg.2008.01.010
13. Gerull B, Heuser A, Wichter T, Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. Nat Genet 2004 36 1162 1164. doi: 10.1038/ng1461
14. van Tintelen JP, Entius MM, Bhuiyan ZA, Plakophilin-2 mutations are the major determinant of familial arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circulation 2006 113 1650 1658. doi: 10.1161/CIRCULATIONAHA.105.609719
15. Chen SN, Gurha P, Lombardi R, Ruggiero A, Willerson JT, Marian AJ, The hippo pathway is activated and is a causal mechanism for adipogenesis in arrhythmogenic cardiomyopathy. Circ Res 2014 114 454 468. doi: 10.1161/CIRCRESAHA.114.302810
16. Garcia-Gras E, Lombardi R, Giocondo MJ, Willerson JT, Schneider MD, Khoury DS, Marian AJ, Suppression of canonical Wnt/beta-catenin signaling by nuclear plakoglobin recapitulates phenotype of arrhythmogenic right ventricular cardiomyopathy. J Clin Invest 2006 116 2012 2021. doi: 10.1172/JCI27751
17. Heallen T, Zhang M, Wang J, Bonilla-Claudio M, Klysik E, Johnson RL, Martin JF, Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size. Science 2011 332 458 461. doi: 10.1126/science.1199010
18. Thum T, Condorelli G, Long noncoding RNAs and microRNAs in cardiovascular pathophysiology. Circ Res 2015 116 751 762. doi: 10.1161/CIRCRESAHA.116.303549
19. Gurha P, Marian AJ, Noncoding RNAs in cardiovascular biology and disease. Circ Res 2013 113 e115 e120. doi: 10.1161/CIRCRESAHA.113.302988
20. Lu TY, Lin B, Li Y, Arora A, Han L, Cui C, Coronnello C, Sheng Y, Benos PV, Yang L, Overexpression of microRNA-1 promotes cardiomyocyte commitment from human cardiovascular progenitors via suppressing WNT and FGF signaling pathways. J Mol Cell Cardiol 2013 63 146 154. doi: 10.1016/j.yjmcc.2013.07.019
21. Bird A, Genome biology: not drowning but waving. Cell 2013 154 951 952. doi: 10.1016/j.cell.2013.08.010
22. Tian Y, Liu Y, Wang T, Zhou N, Kong J, Chen L, Snitow M, Morley M, Li D, Petrenko N, Zhou S, Lu M, Gao E, Koch WJ, Stewart KM, Morrisey EE, A microrna-hippo pathway that promotes cardiomyocyte proliferation and cardiac regeneration in mice. Sci Transl Med 2015 7 279ra238
23. Thompson BJ, Cohen SM, The Hippo pathway regulates the bantam microRNA to control cell proliferation and apoptosis in Drosophila. Cell 2006 126 767 774. doi: 10.1016/j.cell.2006.07.013
24. Kim IM, Wang Y, Park KM, Tang Y, Teoh JP, Vinson J, Traynham CJ, Pironti G, Mao L, Su H, Johnson JA, Koch WJ, Rockman HA, β-Arrestin1-biased β1-Adrenergic receptor signaling regulates microRNA processing. Circ Res 2014 114 833 844. doi: 10.1161/CIRCRESAHA.114.302766
25. Wang D, Zhang H, Li M, Frid MG, Flockton AR, McKeon BA, Yeager ME, Fini MA, Morrell NW, Pullamsetti SS, Velegala S, Seeger W, McKinsey TA, Sucharov CC, Stenmark KR, MicroRNA-124 controls the proliferative, migratory, and inflammatory phenotype of pulmonary vascular fibroblasts. Circ Res 2014 114 67 78. doi: 10.1161/CIRCRESAHA.114.301633
26. Castaldi A, Zaglia T, Di Mauro V, MicroRNA-133 modulates the β1-Adrenergic receptor transduction cascade. Circ Res 2014 115 273 283. doi: 10.1161/CIRCRESAHA.115.303252
27. Harada M, Luo X, Murohara T, Yang B, Dobrev D, Nattel S, MicroRNA regulation and cardiac calcium signaling: role in cardiac disease and therapeutic potential. Circ Res 2014 114 689 705. doi: 10.1161/CIRCRESAHA.114.301798
28. Sun X, He S, Wara AK, Icli B, Shvartz E, Tesmenitsky Y, Belkin N, Li D, Blackwell TS, Sukhova GK, Croce K, Feinberg MW, Systemic delivery of microRNA-181b inhibits nuclear factor-κB activation, vascular inflammation, and atherosclerosis in apolipoprotein E-deficient mice. Circ Res 2014 114 32 40. doi: 10.1161/CIRCRESAHA.113.302089
29. Icli B, Wara AK, Moslehi J, MicroRNA-26a regulates pathological and physiological angiogenesis by targeting BMP/SMAD1 signaling. Circ Res 2013 113 1231 1241. doi: 10.1161/CIRCRESAHA.113.301780
30. Yang Y, Del Re DP, Nakano N, Sciarretta S, Zhai P, Park J, Sayed D, Shirakabe A, Matsushima S, Park Y, Tian B, Abdellatif M, Sadoshima J, miR-206 mediates YAP-induced cardiac hypertrophy and survival. Circ Res 2015 117 891 904. doi: 10.1161/CIRCRESAHA.115.306624
31. Bush EW, van Rooij E, miR-25 in heart failure. Circ Res 2014 115 610 612. doi: 10.1161/CIRCRESAHA.114.304909
32. Kuwabara Y, Horie T, Baba O, Watanabe S, Nishiga M, Usami S, Izuhara M, Nakao T, Nishino T, Otsu K, Kita T, Kimura T, Ono K, MicroRNA-451 exacerbates lipotoxicity in cardiac myocytes and high-fat diet-induced cardiac hypertrophy in mice through suppression of the LKB1/AMPK pathway. Circ Res 2015 116 279 288. doi: 10.1161/CIRCRESAHA.116.304707
33. Li CJ, Cheng P, Liang MK, Chen YS, Lu Q, Wang JY, Xia ZY, Zhou HD, Cao X, Xie H, Liao EY, Luo XH, MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation. J Clin Invest 2015 125 1509 1522. doi: 10.1172/JCI77716
34. Carlson S, Trial J, Soeller C, Entman ML, Cardiac mesenchymal stem cells contribute to scar formation after myocardial infarction. Cardiovasc Res 2011 91 99 107. doi: 10.1093/cvr/cvr061
35. Cieslik KA, Trial J, Entman ML, Defective myofibroblast formation from mesenchymal stem cells in the aging murine heart rescue by activation of the AMPK pathway. Am J Pathol 2011 179 1792 1806. doi: 10.1016/j.ajpath.2011.06.022
36. Lombardi R, Chen SN, Ruggiero A, Gurha P, Czernuszewicz GZ, Willerson JT, Marian AJ, Cardiac fibro-Adipocyte progenitors express desmosome proteins and preferentially differentiate to adipocytes upon deletion of the Desmoplakin gene. Circ Res 2016 119 41 54. doi: 10.1161/CIRCRESAHA.115.308136
37. Lombardi R, da Graca Cabreira-Hansen M, Bell A, Fromm RR, Willerson JT, Marian AJ, Nuclear plakoglobin is essential for differentiation of cardiac progenitor cells to adipocytes in arrhythmogenic right ventricular cardiomyopathy. Circ Res 2011 109 1342 1353. doi: 10.1161/CIRCRESAHA.111.255075
38. Lombardi R, Dong J, Rodriguez G, Bell A, Leung TK, Schwartz RJ, Willerson JT, Brugada R, Marian AJ, Genetic fate mapping identifies second heart field progenitor cells as a source of adipocytes in arrhythmogenic right ventricular cardiomyopathy. Circ Res 2009 104 1076 1084. doi: 10.1161/CIRCRESAHA.109.196899
39. Shukla V, Coumoul X, Wang RH, Kim HS, Deng CX, RNA interference and inhibition of MEK-ERK signaling prevent abnormal skeletal phenotypes in a mouse model of craniosynostosis. Nat Genet 2007 39 1145 1150. doi: 10.1038/ng2096
40. Shukla V, Coumoul X, Deng CX, RNAi-based conditional gene knockdown in mice using a U6 promoter driven vector. Int J Biol Sci 2007 3 91 99
41. Moses KA, DeMayo F, Braun RM, Reecy JL, Schwartz RJ, Embryonic expression of an Nkx2-5/Cre gene using ROSA26 reporter mice. Genesis 2001 31 176 180
42. Yaylaoglu MB, Titmus A, Visel A, Alvarez-Bolado G, Thaller C, Eichele G, Comprehensive expression atlas of fibroblast growth factors and their receptors generated by a novel robotic in situ hybridization platform. Dev Dyn 2005 234 371 386. doi: 10.1002/dvdy.20441
43. Robertson KD, Ait-Si-Ali S, Yokochi T, Wade PA, Jones PL, Wolffe AP, DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters. Nat Genet 2000 25 338 342. doi: 10.1038/77124
44. Sommariva E, Brambilla S, Carbucicchio C, Cardiac mesenchymal stromal cells are a source of adipocytes in arrhythmogenic cardiomyopathy. Eur Heart J 2016 37 1835 1846. doi: 10.1093/eurheartj/ehv579
45. Lombardi R, Marian AJ, Arrhythmogenic right ventricular cardiomyopathy is a disease of cardiac stem cells. Curr Opin Cardiol 2010 25 222 228. doi: 10.1097/HCO.0b013e3283376daf
46. Shalom-Feuerstein R, Serror L, De La Forest Divonne S, Petit I, Aberdam E, Camargo L, Damour O, Vigouroux C, Solomon A, Gaggioli C, Itskovitz-Eldor J, Ahmad S, Aberdam D, Pluripotent stem cell model reveals essential roles for miR-450b-5p and miR-184 in embryonic corneal lineage specification. Stem Cells 2012 30 898 909. doi: 10.1002/stem.1068
47. Liu C, Teng ZQ, Santistevan NJ, Szulwach KE, Guo W, Jin P, Zhao X, Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation. Cell Stem Cell 2010 6 433 444. doi: 10.1016/j.stem.2010.02.017
48. Iovino N, Pane A, Gaul U, miR-184 has multiple roles in Drosophila female germline development. Dev Cell 2009 17 123 133. doi: 10.1016/j.devcel.2009.06.008
49. Wilfling F, Wang H, Haas JT, Triacylglycerol synthesis enzymes mediate lipid droplet growth by relocalizing from the ER to lipid droplets. Dev Cell 2013 24 384 399. doi: 10.1016/j.devcel.2013.01.013
50. Ruan H, Pownall HJ, Overexpression of 1-Acyl-glycerol-3-phosphate acyltransferase-Alpha enhances lipid storage in cellular models of adipose tissue and skeletal muscle. Diabetes 2001 50 233 240
51. Wu GG, Li WH, He WG, Jiang N, Zhang GX, Chen W, Yang HF, Liu QL, Huang YN, Zhang L, Zhang T, Zeng XC, Mir-184 post-Transcriptionally regulates SOX7 expression and promotes cell proliferation in human hepatocellular carcinoma. PLoS One 2014 9 e88796. doi: 10.1371/journal.pone.0088796
52. Nomura T, Kimura M, Horii T, Morita S, Soejima H, Kudo S, Hatada I, MeCP2-dependent repression of an imprinted miR-184 released by depolarization. Hum Mol Genet 2008 17 1192 1199. doi: 10.1093/hmg/ddn011
53. Mertens C, Hofmann I, Wang Z, Teichmann M, Sepehri Chong S, Schnolzer M, Franke WW, Nuclear particles containing rna polymerase iii complexes associated with the junctional plaque protein plakophilin 2. Proc Natl Acad Sci U S A 2001 98 7795 7800
54. Chen X, Bonne S, Hatzfeld M, van Roy F, Green KJ, Protein binding and functional characterization of plakophilin 2. Evidence for its diverse roles in desmosomes and beta-catenin signaling. J Biol Chem 2002 277 10512 10522. doi: 10.1074/jbc.M108765200
55. Takahashi Y, Chen Q, Rajala RV, Ma JX, MicroRNA-184 modulates canonical Wnt signaling through the regulation of frizzled-7 expression in the retina with ischemia-induced neovascularization. FEBS Lett 2015 589 1143 1149. doi: 10.1016/j.febslet.2015.03.010