J D Molkentin

Summary

Affiliation: Children's Hospital Medical Center
Country: USA

Publications

  1. ncbi Periostin is required for maturation and extracellular matrix stabilization of noncardiomyocyte lineages of the heart
    Paige Snider
    Cardiovascular Development Group, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, USA
    Circ Res 102:752-60. 2008
  2. ncbi Calcineurin and beyond: cardiac hypertrophic signaling
    J D Molkentin
    Department of Pediatrics, University of Cincinnati, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, Cincinnati, Ohio, USA
    Circ Res 87:731-8. 2000
  3. ncbi The zinc finger-containing transcription factors GATA-4, -5, and -6. Ubiquitously expressed regulators of tissue-specific gene expression
    J D Molkentin
    Department of Pediatrics, University of Cincinnati, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA
    J Biol Chem 275:38949-52. 2000
  4. ncbi Calcineurin promotes protein kinase C and c-Jun NH2-terminal kinase activation in the heart. Cross-talk between cardiac hypertrophic signaling pathways
    L J De Windt
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 275:13571-9. 2000
  5. ncbi Direct activation of a GATA6 cardiac enhancer by Nkx2.5: evidence for a reinforcing regulatory network of Nkx2.5 and GATA transcription factors in the developing heart
    J D Molkentin
    Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio, 45229 3039, USA
    Dev Biol 217:301-9. 2000
  6. ncbi The transcription factor GATA4 is activated by extracellular signal-regulated kinase 1- and 2-mediated phosphorylation of serine 105 in cardiomyocytes
    Q Liang
    Department of Pediatrics, Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229 3039, USA
    Mol Cell Biol 21:7460-9. 2001
  7. ncbi Hypertrophic defect unmasked by calcineurin expression in asymptomatic tropomodulin overexpressing transgenic mice
    M A Sussman
    The Children s Hospital and Research Foundation, Division of Molecular Cardiovascular Biology, Room 3033, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
    Cardiovasc Res 46:90-101. 2000
  8. ncbi Targeted inhibition of calcineurin prevents agonist-induced cardiomyocyte hypertrophy
    T Taigen
    Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    Proc Natl Acad Sci U S A 97:1196-201. 2000
  9. ncbi The dual-specificity phosphatase MKP-1 limits the cardiac hypertrophic response in vitro and in vivo
    O F Bueno
    Department of Pediatrics, University of Cincinnati, Children's Hospital Medical Center, Division of Molecular Cardiovascular Biology, Cincinnati, Ohio, USA
    Circ Res 88:88-96. 2001
  10. ncbi The transcription factors GATA4 and GATA6 regulate cardiomyocyte hypertrophy in vitro and in vivo
    Q Liang
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 276:30245-53. 2001

Collaborators

Detail Information

Publications81

  1. ncbi Periostin is required for maturation and extracellular matrix stabilization of noncardiomyocyte lineages of the heart
    Paige Snider
    Cardiovascular Development Group, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, USA
    Circ Res 102:752-60. 2008
    ..Thus, peri(lacZ) knockouts provide a new model of viable latent valve disease...
  2. ncbi Calcineurin and beyond: cardiac hypertrophic signaling
    J D Molkentin
    Department of Pediatrics, University of Cincinnati, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, Cincinnati, Ohio, USA
    Circ Res 87:731-8. 2000
    ....
  3. ncbi The zinc finger-containing transcription factors GATA-4, -5, and -6. Ubiquitously expressed regulators of tissue-specific gene expression
    J D Molkentin
    Department of Pediatrics, University of Cincinnati, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA
    J Biol Chem 275:38949-52. 2000
  4. ncbi Calcineurin promotes protein kinase C and c-Jun NH2-terminal kinase activation in the heart. Cross-talk between cardiac hypertrophic signaling pathways
    L J De Windt
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 275:13571-9. 2000
    ..Collectively, these data indicate that calcineurin hypertrophic signaling is interconnected with PKCalpha, theta, and JNK in the heart, while PKCepsilon, beta, lambda, p38, and ERK1/2 are not involved in calcineurin-mediated hypertrophy...
  5. ncbi Direct activation of a GATA6 cardiac enhancer by Nkx2.5: evidence for a reinforcing regulatory network of Nkx2.5 and GATA transcription factors in the developing heart
    J D Molkentin
    Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio, 45229 3039, USA
    Dev Biol 217:301-9. 2000
    ..These studies demonstrate that GATA6 is a direct target gene for Nkx2.5 in the developing heart and reveal a mutually reinforcing regulatory network of Nkx2.5 and GATA transcription factors during cardiogenesis...
  6. ncbi The transcription factor GATA4 is activated by extracellular signal-regulated kinase 1- and 2-mediated phosphorylation of serine 105 in cardiomyocytes
    Q Liang
    Department of Pediatrics, Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229 3039, USA
    Mol Cell Biol 21:7460-9. 2001
    ....
  7. ncbi Hypertrophic defect unmasked by calcineurin expression in asymptomatic tropomodulin overexpressing transgenic mice
    M A Sussman
    The Children s Hospital and Research Foundation, Division of Molecular Cardiovascular Biology, Room 3033, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
    Cardiovasc Res 46:90-101. 2000
    ..Dilation and hypertrophy often occur concurrently in cardiomyopathy, yet the interaction between these two functionally distinct conditions remains unknown...
  8. ncbi Targeted inhibition of calcineurin prevents agonist-induced cardiomyocyte hypertrophy
    T Taigen
    Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    Proc Natl Acad Sci U S A 97:1196-201. 2000
    ....
  9. ncbi The dual-specificity phosphatase MKP-1 limits the cardiac hypertrophic response in vitro and in vivo
    O F Bueno
    Department of Pediatrics, University of Cincinnati, Children's Hospital Medical Center, Division of Molecular Cardiovascular Biology, Cincinnati, Ohio, USA
    Circ Res 88:88-96. 2001
    ....
  10. ncbi The transcription factors GATA4 and GATA6 regulate cardiomyocyte hypertrophy in vitro and in vivo
    Q Liang
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 276:30245-53. 2001
    ..Expression of GATA4-engrailed blocked GATA4- and GATA6-directed transcriptional responses and agonist-induced cardiomyocyte hypertrophy, demonstrating that cardiac-expressed GATA factors are necessary mediators of this process...
  11. ncbi Targeted inhibition of calcineurin attenuates cardiac hypertrophy in vivo
    L J De Windt
    Divisions of Molecular Cardiovascular Biology and Cardiology, Department of Pediatrics, Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
    Proc Natl Acad Sci U S A 98:3322-7. 2001
    ..These results provide genetic evidence implicating calcineurin as an important mediator of the cardiac hypertrophic response in vivo...
  12. ncbi Enhanced Ca2+ channel currents in cardiac hypertrophy induced by activation of calcineurin-dependent pathway
    A Yatani
    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
    J Mol Cell Cardiol 33:249-59. 2001
    ..Taken together these data suggest that chronic activation of calcineurin is associated with myocyte hypertrophy and a secondary enhancement of intracellular Ca2+ handling that is tied to the hypertrophy response itself...
  13. ncbi Calcineurin enhances MAPK phosphatase-1 expression and p38 MAPK inactivation in cardiac myocytes
    H W Lim
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 276:15913-9. 2001
    ..These data suggest that calcineurin enhances MKP-1 expression in cardiac myocytes, which is associated with p38 inactivation...
  14. ncbi Temporally regulated and tissue-specific gene manipulations in the adult and embryonic heart using a tamoxifen-inducible Cre protein
    D S Sohal
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Division of Molecular Cardiovascular Biology, Cincinnati, Ohio, USA
    Circ Res 89:20-5. 2001
    ....
  15. ncbi Divergent transcriptional responses to independent genetic causes of cardiac hypertrophy
    B J Aronow
    Department of Developmental Biology, Children s Hospital Research Center, Cincinnati, OH 45229, USA
    Physiol Genomics 6:19-28. 2001
    ....
  16. ncbi Cytoplasmic signaling pathways that regulate cardiac hypertrophy
    J D Molkentin
    Department of Pediatrics, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229 3039, USA
    Annu Rev Physiol 63:391-426. 2001
    ..Each of these signaling pathways has been implicated as a hypertrophic transducer, which collectively suggests an emerging paradigm whereby multiple pathways operate in concert to orchestrate a hypertrophic response..
  17. ncbi Retinoic acid inhibits cardiac neural crest migration by blocking c-Jun N-terminal kinase activation
    J Li
    Division of Molecular Cardiovascular Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA
    Dev Biol 232:351-61. 2001
    ..These data demonstrate that the JNK signaling pathway and c-Jun activation are critical for cardiac neural crest outgrowth and are potential targets for the action of RA...
  18. ncbi The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice
    O F Bueno
    Department of Pediatrics, University of Cincinnati, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    EMBO J 19:6341-50. 2000
    ..The results of the present study indicate that the MEK1-ERK1/2 signaling pathway stimulates a physiologic hypertrophy response associated with augmented cardiac function and partial resistance to apoptotsis...
  19. ncbi MEF2B is a component of a smooth muscle-specific complex that binds an A/T-rich element important for smooth muscle myosin heavy chain gene expression
    Y Katoh
    Section of Molecular Cardiology, University of Cincinnati, Ohio 45267, USA
    J Biol Chem 273:1511-8. 1998
    ..This is the first report demonstrating a role for MEF2 factors in smooth muscle-specific gene expression...
  20. ncbi Pathogenesis of dilated cardiomyopathy: molecular, structural, and population analyses in tropomodulin-overexpressing transgenic mice
    M A Sussman
    Division of Molecular Cardiovascular Biology, Children s Hospital and Research Foundation, Cincinnati, Ohio 45229, USA
    Am J Pathol 155:2101-13. 1999
    ....
  21. ncbi Periostin facilitates eosinophil tissue infiltration in allergic lung and esophageal responses
    C Blanchard
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    Mucosal Immunol 1:289-96. 2008
    ....
  22. ncbi Cardiomyocyte GATA4 functions as a stress-responsive regulator of angiogenesis in the murine heart
    Joerg Heineke
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229, USA
    J Clin Invest 117:3198-210. 2007
    ..To our knowledge, these results demonstrate [corrected] a previously unrecognized function for GATA4 as a regulator of cardiac angiogenesis through a nonhypoxic, load, and/or disease-responsive mechanism...
  23. ncbi Calcineurin/NFAT coupling participates in pathological, but not physiological, cardiac hypertrophy
    Benjamin J Wilkins
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Children s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, Ohio 45229 3039, USA
    Circ Res 94:110-8. 2004
    ....
  24. ncbi Calcineurin Abeta gene targeting predisposes the myocardium to acute ischemia-induced apoptosis and dysfunction
    Orlando F Bueno
    Department of Pediatrics, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    Circ Res 94:91-9. 2004
    ..These results represent the first genetic loss-of-function data showing a prosurvival role for calcineurin-NFAT signaling in the heart...
  25. ncbi Requirement of transcription factor NFAT in developing atrial myocardium
    William Schubert
    Dept of Molecular Pharmacology, Albert Einstein College of Medicine, Jack and Pearl Resnick Campus, Bronx, NY 10461, USA
    J Cell Biol 161:861-74. 2003
    ..Thus, regulation of cytoskeletal protein gene expression by NFAT may be important for the structural architecture of the developing atrial myocardium...
  26. ncbi Targeted inhibition of p38 MAPK promotes hypertrophic cardiomyopathy through upregulation of calcineurin-NFAT signaling
    Julian C Braz
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio, USA
    J Clin Invest 111:1475-86. 2003
    ..Collectively, these observations indicate that reduced p38 signaling in the heart promotes myocyte growth through a mechanism involving enhanced calcineurin-NFAT signaling...
  27. ncbi Calcineurin-NFAT signaling regulates the cardiac hypertrophic response in coordination with the MAPKs
    Jeffery D Molkentin
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    Cardiovasc Res 63:467-75. 2004
    ..Thus, an emerging paradigm suggests that calcineurin-NFAT and MAPK signaling pathways are inter-dependent and together orchestrate the cardiac hypertrophic response...
  28. ncbi Calcium-calcineurin signaling in the regulation of cardiac hypertrophy
    Benjamin J Wilkins
    Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229 3039, USA
    Biochem Biophys Res Commun 322:1178-91. 2004
    ..Finally, we will discuss emerging theories as to the mechanisms whereby alterations in intracellular calcium handling might stimulate calcineurin within the context of a contractile cell continually experiencing calcium flux...
  29. ncbi Genetic manipulation of periostin expression reveals a role in cardiac hypertrophy and ventricular remodeling
    Toru Oka
    Department of Pediatrics, University of Cincinnati, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, Cincinnati, OH 45229 3039, USA
    Circ Res 101:313-21. 2007
    ..These are the first genetic data detailing the function of Pn in the adult heart as a regulator of cardiac remodeling and hypertrophy...
  30. ncbi Direct and indirect interactions between calcineurin-NFAT and MEK1-extracellular signal-regulated kinase 1/2 signaling pathways regulate cardiac gene expression and cellular growth
    Bastiano Sanna
    Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Ave, MLC7020, Cincinnati, OH 45229 3039, USA
    Mol Cell Biol 25:865-78. 2005
    ..Collectively, these results indicate that calcineurin-NFAT and MEK1-ERK1/2 pathways constitute a codependent signaling module in cardiomyocytes that coordinately regulates the growth response through two distinct mechanisms...
  31. ncbi Regulation of calcineurin through transcriptional induction of the calcineurin A beta promoter in vitro and in vivo
    Toru Oka
    Cincinnati Children s Hospital Medical Center, Division of Molecular Cardiovascular Biology, 3333 Burnet Ave, MLC7020, Cincinnati OH 45229 3039, USA
    Mol Cell Biol 25:6649-59. 2005
    ....
  32. ncbi The DnaJ-related factor Mrj interacts with nuclear factor of activated T cells c3 and mediates transcriptional repression through class II histone deacetylase recruitment
    Yan Shan Dai
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Division of Molecular Cardiovascular Biology, 3333 Burnet Ave, MLC7020, Cincinnati, Ohio 45229 3039, USA
    Mol Cell Biol 25:9936-48. 2005
    ..Collectively, our results define a novel response pathway whereby NFATc3 is negatively regulated by class II histone deacetylases through the DnaJ (heat shock protein-40) superfamily member Mrj...
  33. ncbi Regulation of cardiac hypertrophy by intracellular signalling pathways
    Joerg Heineke
    Department of Pediatrics, University of Cincinnati, Children's Hospital Medical Center, Division of Molecular Cardiovascular Biology, 3333 Burnet Ave, Cincinnati, Ohio 45229, USA
    Nat Rev Mol Cell Biol 7:589-600. 2006
    ..Recent findings in genetically modified animal models implicate important intermediate signal-transduction pathways in the coordination of heart growth following physiological and pathological stimulation...
  34. ncbi Cardiac-specific deletion of Gata4 reveals its requirement for hypertrophy, compensation, and myocyte viability
    Toru Oka
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Ohio 45229 3039, USA
    Circ Res 98:837-45. 2006
    ..Thus, GATA4 is a necessary regulator of cardiac gene expression, hypertrophy, stress-compensation, and myocyte viability...
  35. ncbi NFATc3 and NFATc4 are required for cardiac development and mitochondrial function
    Paul B Bushdid
    Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center Cincinnati, ML 7020, 3333 Burnet Ave, Cincinnati, Ohio 45229, USA
    Circ Res 92:1305-13. 2003
    ..Together, these data support the hypothesis that loss of NFAT activity in the heart results in a deficiency in mitochondrial energy metabolism required for cardiac morphogenesis and function...
  36. ncbi A friend within the heart: natriuretic peptide receptor signaling
    Jeffery D Molkentin
    Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA
    J Clin Invest 111:1275-7. 2003
  37. ncbi Targeted disruption of NFATc3, but not NFATc4, reveals an intrinsic defect in calcineurin-mediated cardiac hypertrophic growth
    Benjamin J Wilkins
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Children s Hospital Medical Center, Cincinnati Ohio 45229 3039, USA
    Mol Cell Biol 22:7603-13. 2002
    ..NFATc3-null mice also demonstrated attenuated pressure overload- and angiotensin II-induced cardiac hypertrophy. These results provide genetic evidence that calcineurin-regulated responses require NFAT effectors in vivo...
  38. ncbi Calcineurin transgenic mice have mitochondrial dysfunction and elevated superoxide production
    M R Sayen
    The Scripps Research Institute, La Jolla, California 92037, USA
    Am J Physiol Cell Physiol 284:C562-70. 2003
    ..Taken together, these data indicate that calcineurin signaling affects mitochondrial energetics and superoxide production. The excessive production of superoxide may contribute to the development of cardiac failure...
  39. ncbi Calcineurin and NFAT4 induce chondrogenesis
    Masuhiro Tomita
    Department of Pathology, University of Texas Health Science Center, San Antonio 78229, USA
    J Biol Chem 277:42214-8. 2002
    ..Furthermore, activated NFAT4 induced BMP2 gene expression. These results have important implications for the effects of NFATs during development and adaptive responses...
  40. ncbi Is nuclear factor kappaB an attractive therapeutic target for treating cardiac hypertrophy?
    Nicole H Purcell
    Circulation 108:638-40. 2003
  41. ncbi Divergent signaling pathways converge on GATA4 to regulate cardiac hypertrophic gene expression
    Qiangrong Liang
    J Mol Cell Cardiol 34:611-6. 2002
  42. ncbi Requirement of nuclear factor of activated T-cells in calcineurin-mediated cardiomyocyte hypertrophy
    Eva van Rooij
    Department of Cardiology, Cardiovascular Research Institute Maastricht, University Hospital, P Debyelaan 25, The Netherlands
    J Biol Chem 277:48617-26. 2002
    ..These results indicate that multiple NFAT isoforms are expressed in cardiomyocytes where they function as necessary transducers of calcineurin in facilitating cardiomyocyte hypertrophy...
  43. ncbi Temporal activation of c-Jun N-terminal kinase in adult transgenic heart via cre-loxP-mediated DNA recombination
    Brian G Petrich
    Department of Physiology, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA
    FASEB J 17:749-51. 2003
    ..Our data also demonstrated that the inducible gene-switch approach reported here may also be applicable in other studies to achieve efficient, tissue-specific, and temporally regulated genetic manipulation in intact animals...
  44. ncbi Inhibition of calcineurin-NFAT hypertrophy signaling by cGMP-dependent protein kinase type I in cardiac myocytes
    Beate Fiedler
    Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany
    Proc Natl Acad Sci U S A 99:11363-8. 2002
    ..Inhibition of calcineurin-NFAT signaling by PKG I provides a framework for understanding how NO inhibits cardiac myocyte hypertrophy...
  45. ncbi The transcription factors GATA4 and dHAND physically interact to synergistically activate cardiac gene expression through a p300-dependent mechanism
    Yan Shan Dai
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 277:24390-8. 2002
    ....
  46. ncbi Calcineurin increases cardiac transient outward K+ currents via transcriptional up-regulation of Kv4.2 channel subunits
    Nanling Gong
    Departments of Physiology and Medicine, Heart and Stroke/Richard Lewar Centre of Excellence, University Health Network, University of Toronto, 150 College Street, Toronto, Ontario M5S 3E2, Canada
    J Biol Chem 281:38498-506. 2006
    ..This positive regulation of Kv4.2 transcription by Cn activation is expected to minimize the reductions in I(to,f) and Kv4.2 expression observed in hypertrophic cardiomyocytes...
  47. ncbi Does contractile Ca2+ control calcineurin-NFAT signaling and pathological hypertrophy in cardiac myocytes?
    Steven R Houser
    Department of Physiology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA
    Sci Signal 1:pe31. 2008
    ..Here, we critically review evidence that supports the hypothesis that calcineurin-NFAT signaling is regulated by contractile Ca(2+) transients in cardiac myocytes...
  48. ncbi Conditional dicer gene deletion in the postnatal myocardium provokes spontaneous cardiac remodeling
    Paula A da Costa Martins
    Department of Medical Physiology, University Medical Center Utrecht, Utrecht, Netherlands
    Circulation 118:1567-76. 2008
    ..Dicer, an RNAse III endonuclease critical for processing of pre-microRNAs (miRNAs) into mature 22-nucleotide miRNAs, has proven a useful target to dissect the significance of miRNAs biogenesis in mammalian biology...
  49. ncbi Calcineurin regulates NFAT-dependent iNOS expression and protection of cardiomyocytes: co-operation with Src tyrosine kinase
    Kofo Obasanjo-Blackshire
    Cardiovascular Division, King's College London School of Medicine, Department of Cardiology, The Rayne Institute, St Thomas's Hospital, Lambeth Palace Road, London SE1 7EH, UK
    Cardiovasc Res 71:672-83. 2006
    ..CONCLUSIONS: These results support a cardioprotective role for calcineurin mediated by NFAT-dependent induction of iNOS expression and co-operativity between calcineurin and Src...
  50. ncbi Pharmacological- and gene therapy-based inhibition of protein kinase Calpha/beta enhances cardiac contractility and attenuates heart failure
    Michael Hambleton
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    Circulation 114:574-82. 2006
    ....
  51. ncbi Calcineurin-dependent cardiomyopathy is activated by TRPC in the adult mouse heart
    Hiroyuki Nakayama
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio, USA
    FASEB J 20:1660-70. 2006
    ..Thus, enhanced store-operated Ca2+ entry in the heart can regulate calcineurin-NFAT signaling in vivo, which could secondarily impact the hypertrophic response and cardiomyopathy...
  52. ncbi A redox-dependent pathway for regulating class II HDACs and cardiac hypertrophy
    Tetsuro Ago
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA
    Cell 133:978-93. 2008
    ..Our study reveals a novel regulatory mechanism of cardiac hypertrophy through which the nucleocytoplasmic shuttling of class II HDACs is modulated by their redox modification in a Trx1-sensitive manner...
  53. ncbi Mediating ERK 1/2 signaling rescues congenital heart defects in a mouse model of Noonan syndrome
    Tomoki Nakamura
    Cincinnati Children s Hospital Medical Center, The Children s Hospital Research Foundation, Division of Molecular Cardiovascular Biology, Cincinnati, Ohio 45229 3039, USA
    J Clin Invest 117:2123-32. 2007
    ....
  54. ncbi Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates muscular dystrophy
    Douglas P Millay
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
    Nat Med 14:442-7. 2008
    ..Thus, mitochondrial-dependent necrosis represents a prominent disease mechanism in muscular dystrophy, suggesting that inhibition of cyclophilin D could provide a new pharmacologic treatment strategy for these diseases...
  55. ncbi Nuclear Dbf2-related protein kinases (NDRs) in isolated cardiac myocytes and the myocardium: activation by cellular stresses and by phosphoprotein serine-/threonine-phosphatase inhibitors
    Stephen J Fuller
    National Heart and Lung Institute NHLI Division, Faculty of Medicine, Imperial College London, Flowers Building, Armstrong Road, London SW7 2AZ, UK
    Cell Signal 20:1564-77. 2008
    ..From a pathological viewpoint, we conclude that activities of NDR1 and NDR2 are responsive to cytotoxic stresses in heart preparations and this may represent a previously-unidentified response to myocardial ischaemia in vivo...
  56. ncbi Analysis of the transcriptional activity of endogenous NFAT5 in primary cells using transgenic NFAT-luciferase reporter mice
    Beatriz Morancho
    Immunology Unit, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
    BMC Mol Biol 9:13. 2008
    ..Since the NFAT site of this reporter was very similar to an optimal NFAT5 site, we tested whether this reporter could detect the activation of NFAT5 in transgenic cells...
  57. ncbi Calcineurin-induced energy wasting in a transgenic mouse model of heart failure
    Ilka Pinz
    NMR Laboratory for Physiological Chemistry, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    Am J Physiol Heart Circ Physiol 294:H1459-66. 2008
    ....
  58. ncbi Inducible and myocyte-specific inhibition of PKCalpha enhances cardiac contractility and protects against infarction-induced heart failure
    Michael Hambleton
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    Am J Physiol Heart Circ Physiol 293:H3768-71. 2007
    ..Thus, myocyte autonomous inhibition of PKCalpha protects the adult heart from decompensation and dilated cardiomyopathy after infarction injury in association with a primary enhancement in contractility...
  59. ncbi Genetic inhibition of cardiac ERK1/2 promotes stress-induced apoptosis and heart failure but has no effect on hypertrophy in vivo
    Nicole H Purcell
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
    Proc Natl Acad Sci U S A 104:14074-9. 2007
    ..Thus, ERK1/2 signaling is not required for mediating physiologic or pathologic cardiac hypertrophy in vivo, although it does play a protective role in response to pathologic stimuli...
  60. ncbi Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury
    Patrick C H Hsieh
    Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA
    Nat Med 13:970-4. 2007
    ..5% in areas bordering a myocardial infarction, 76.6% in areas away from a myocardial infarction, and 75.7% in hearts subjected to pressure overload, indicating that stem cells or precursor cells had refreshed the cardiomyocytes...
  61. ncbi Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure
    Hiroyuki Nakayama
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA
    J Clin Invest 117:2431-44. 2007
    ....
  62. ncbi The beta-catenin/T-cell factor/lymphocyte enhancer factor signaling pathway is required for normal and stress-induced cardiac hypertrophy
    Xin Chen
    Molecular Cardiology Research Institute, Tufts New England Medical Center and Tufts University School of Medicine, USA
    Mol Cell Biol 26:4462-73. 2006
    ..Thus, our studies, employing complementary models in vivo, implicate beta-catenin/Tcf/Lef signaling as an essential growth-regulatory pathway in terminally differentiated cells...
  63. ncbi Extracellular signal-regulated kinase 2 interacts with and is negatively regulated by the LIM-only protein FHL2 in cardiomyocytes
    Nicole H Purcell
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    Mol Cell Biol 24:1081-95. 2004
    ..Collectively, these results suggest that FHL2 serves a repressor function in cardiomyocytes through its ability to inhibit ERK1/2 transcriptional coupling...
  64. ncbi Redefining the roles of p38 and JNK signaling in cardiac hypertrophy: dichotomy between cultured myocytes and animal models
    Qiangrong Liang
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA
    J Mol Cell Cardiol 35:1385-94. 2003
    ..However, SAPK signaling is likely maladaptive, despite its putative anti-hypertrophic role in vivo, given the observation of dilated cardiomyopathy and heart failure in gain-of-function transgenic models...
  65. ncbi c-Jun N-terminal kinases (JNK) antagonize cardiac growth through cross-talk with calcineurin-NFAT signaling
    Qiangrong Liang
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    EMBO J 22:5079-89. 2003
    ..These results also suggest that myocardial JNK activation is primarily dedicated to modulating calcineurin-NFAT signaling in the regulation of differentiated heart growth...
  66. ncbi Activation of GATA-4 by serotonin in pulmonary artery smooth muscle cells
    Yuichiro J Suzuki
    Department of Medicine, Tufts University, Boston, Massachusetts 02111, USA
    J Biol Chem 278:17525-31. 2003
    ..Thus, GATA-4 mediates 5-HT-induced growth of PASMC and may be an important therapeutic target for the prevention of pulmonary hypertension...
  67. ncbi Involvement of extracellular signal-regulated kinases 1/2 in cardiac hypertrophy and cell death
    Orlando F Bueno
    Department of Pediatrics, University of Cincinnati, Division of Molecular Cardiovascular Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA
    Circ Res 91:776-81. 2002
    ....
  68. ncbi Defective T cell development and function in calcineurin A beta -deficient mice
    Orlando F Bueno
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    Proc Natl Acad Sci U S A 99:9398-403. 2002
    ..These results establish a critical role for CnA beta signaling in regulating T cell development and activation in vivo...
  69. ncbi Calcineurin and hypertrophic heart disease: novel insights and remaining questions
    Orlando F Bueno
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati OH, USA
    Cardiovasc Res 53:806-21. 2002
    ....
  70. ncbi Reduction of I(to) causes hypertrophy in neonatal rat ventricular myocytes
    Zamaneh Kassiri
    Department of Physiology, Heart and Stroke/Richard Lewar Center, University of Toronto, Toronto, Canada
    Circ Res 90:578-85. 2002
    ..2)N infection were prevented by blocking Ca2+ entry and excitability with verapamil or high [K+]o. Our studies suggest that reductions of K(v4.2/3)-based I(to) play a role in hypertrophy signaling by activation of calcineurin...
  71. ncbi DSCR1 gene expression is dependent on NFATc1 during cardiac valve formation and colocalizes with anomalous organ development in trisomy 16 mice
    Alexander W Lange
    Division of Molecular Cardiovascular Biology, Children s Medical Center Cincinnati ML 7020, Cincinnati, OH 45229, USA
    Dev Biol 266:346-60. 2004
    ....
  72. ncbi Targeted inhibition of p38 mitogen-activated protein kinase antagonizes cardiac injury and cell death following ischemia-reperfusion in vivo
    Robert A Kaiser
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Division of Molecular Cardiovascular Biology, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 279:15524-30. 2004
    ..Collectively, these results indicate that p38 functions as a pro-death signaling effector in both cultured myocytes as well as in the intact heart...
  73. ncbi Direct interaction and reciprocal regulation between ASK1 and calcineurin-NFAT control cardiomyocyte death and growth
    Qinghang Liu
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, 3333 Burnet Ave, MLC7020, Cincinnati Ohio 45229 3039, USA
    Mol Cell Biol 26:3785-97. 2006
    ....
  74. ncbi GDF15/MIC-1 functions as a protective and antihypertrophic factor released from the myocardium in association with SMAD protein activation
    Jian Xu
    Department of Pediatrics, University of Cincinnati, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, Ohio 45229 3039, USA
    Circ Res 98:342-50. 2006
    ..These results identify GDF15 as a novel autocrine/endocrine factor that antagonizes the hypertrophic response and loss of ventricular performance, possibly through a mechanism involving SMAD proteins...
  75. ncbi Induced deletion of the N-cadherin gene in the heart leads to dissolution of the intercalated disc structure
    Igor Kostetskii
    Center for Research on Reproduction and Women s Health, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Circ Res 96:346-54. 2005
    ....
  76. ncbi Identification of a cooperative mechanism involving interleukin-13 and eotaxin-2 in experimental allergic lung inflammation
    Samuel M Pope
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    J Biol Chem 280:13952-61. 2005
    ..Taken together, these results demonstrate a cooperative mechanism between IL-13 and eotaxin-2. In particular, IL-13 mediates allergen-induced eotaxin-2 expression, and eotaxin-2 mediates IL-13-induced airway eosinophilia...
  77. ncbi Cardiomyocytes fuse with surrounding noncardiomyocytes and reenter the cell cycle
    Katsuhisa Matsuura
    Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
    J Cell Biol 167:351-63. 2004
    ..These results suggest that cardiomyocytes fuse with other cells and enter the cell cycle by maintaining their phenotypes...
  78. ncbi MEK1-ERK2 signaling pathway protects myocardium from ischemic injury in vivo
    Daniel J Lips
    Department of Cardiology, Maastricht University, and Heart Lung Center Utrecht, Maastricht and Utrecht, Netherlands
    Circulation 109:1938-41. 2004
    ..Specifically, activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) has been associated with cardioprotection, likely through antagonism of apoptotic regulatory pathways...
  79. ncbi Glycogen synthase kinase-3beta regulates growth, calcium homeostasis, and diastolic function in the heart
    Ashour Michael
    Boston University Medical Center and School of Medicine, Boston, MA 02118, USA
    J Biol Chem 279:21383-93. 2004
    ..Because down-regulation of SERCA2a plays a central role in the diastolic and systolic dysfunction of patients with heart failure, these findings have potential implications for the therapy of this disorder...
  80. ncbi PKC-alpha regulates cardiac contractility and propensity toward heart failure
    Julian C Braz
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    Nat Med 10:248-54. 2004
    ..Thus, PKC-alpha functions as a nodal integrator of cardiac contractility by sensing intracellular Ca(2+) and signal transduction events, which can profoundly affect propensity toward heart failure...
  81. ncbi PKC alpha regulates the hypertrophic growth of cardiomyocytes through extracellular signal-regulated kinase1/2 (ERK1/2)
    Julian C Braz
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    J Cell Biol 156:905-19. 2002
    ..These results implicate PKC alpha as a necessary mediator of cardiomyocyte hypertrophic growth, in part, through a ERK1/2-dependent signaling pathway...