Research ExplorerPublicationsNfat and miR-25 cooperate to reactivate the transcription fa...

Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure

Standard

Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure. / Dirkx, Ellen; Gladka, Monika M; Philippen, Leonne E; Armand, Anne-Sophie; Kinet, Virginie; Leptidis, Stefanos; El Azzouzi, Hamid; Salic, Kanita; Bourajjaj, Meriem; da Silva, Gustavo J J; Olieslagers, Servé; van der Nagel, Roel; de Weger, Roel; Bitsch, Nicole; Kisters, Natasja; Seyen, Sandrine; Morikawa, Yuka; Chanoine, Christophe; Heymans, Stephane; Volders, Paul G A; Thum, Thomas; Dimmeler, Stefanie; Cserjesi, Peter; Eschenhagen, Thomas; da Costa Martins, Paula A; De Windt, Leon J.

In: NAT CELL BIOL, Vol. 15, No. 11, 01.11.2013, p. 1282-93.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Dirkx, E, Gladka, MM, Philippen, LE, Armand, A-S, Kinet, V, Leptidis, S, El Azzouzi, H, Salic, K, Bourajjaj, M, da Silva, GJJ, Olieslagers, S, van der Nagel, R, de Weger, R, Bitsch, N, Kisters, N, Seyen, S, Morikawa, Y, Chanoine, C, Heymans, S, Volders, PGA, Thum, T, Dimmeler, S, Cserjesi, P, Eschenhagen, T, da Costa Martins, PA & De Windt, LJ 2013, 'Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure', NAT CELL BIOL, vol. 15, no. 11, pp. 1282-93. https://doi.org/10.1038/ncb2866

APA

Dirkx, E., Gladka, M. M., Philippen, L. E., Armand, A-S., Kinet, V., Leptidis, S., El Azzouzi, H., Salic, K., Bourajjaj, M., da Silva, G. J. J., Olieslagers, S., van der Nagel, R., de Weger, R., Bitsch, N., Kisters, N., Seyen, S., Morikawa, Y., Chanoine, C., Heymans, S., ... De Windt, L. J. (2013). Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure. NAT CELL BIOL, 15(11), 1282-93. https://doi.org/10.1038/ncb2866

Vancouver

Dirkx E, Gladka MM, Philippen LE, Armand A-S, Kinet V, Leptidis S et al. Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure. NAT CELL BIOL. 2013 Nov 1;15(11):1282-93. https://doi.org/10.1038/ncb2866

Bibtex

@article{0c63aa0f0cb3417793d22c52386f9327,
title = "Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure",
abstract = "Although aberrant reactivation of embryonic gene programs is intricately linked to pathological heart disease, the transcription factors driving these gene programs remain ill-defined. Here we report that increased calcineurin/Nfat signalling and decreased miR-25 expression integrate to re-express the basic helix-loop-helix (bHLH) transcription factor dHAND (also known as Hand2) in the diseased human and mouse myocardium. In line, mutant mice overexpressing Hand2 in otherwise healthy heart muscle cells developed a phenotype of pathological hypertrophy. Conversely, conditional gene-targeted Hand2 mice demonstrated a marked resistance to pressure-overload-induced hypertrophy, fibrosis, ventricular dysfunction and induction of a fetal gene program. Furthermore, in vivo inhibition of miR-25 by a specific antagomir evoked spontaneous cardiac dysfunction and sensitized the murine myocardium to heart failure in a Hand2-dependent manner. Our results reveal that signalling cascades integrate with microRNAs to induce the expression of the bHLH transcription factor Hand2 in the postnatal mammalian myocardium with impact on embryonic gene programs in heart failure.",
keywords = "Animals, Base Sequence, Basic Helix-Loop-Helix Transcription Factors, Gene Expression Profiling, Gene Silencing, Heart Failure, Humans, Mice, Mice, Knockout, MicroRNAs, NFATC Transcription Factors, RNA Processing, Post-Transcriptional, Sequence Homology, Nucleic Acid, Transcription, Genetic",
author = "Ellen Dirkx and Gladka, {Monika M} and Philippen, {Leonne E} and Anne-Sophie Armand and Virginie Kinet and Stefanos Leptidis and {El Azzouzi}, Hamid and Kanita Salic and Meriem Bourajjaj and {da Silva}, {Gustavo J J} and Serv{\'e} Olieslagers and {van der Nagel}, Roel and {de Weger}, Roel and Nicole Bitsch and Natasja Kisters and Sandrine Seyen and Yuka Morikawa and Christophe Chanoine and Stephane Heymans and Volders, {Paul G A} and Thomas Thum and Stefanie Dimmeler and Peter Cserjesi and Thomas Eschenhagen and {da Costa Martins}, {Paula A} and {De Windt}, {Leon J}",
year = "2013",
month = nov,
day = "1",
doi = "10.1038/ncb2866",
language = "English",
volume = "15",
pages = "1282--93",
journal = "NAT CELL BIOL",
issn = "1465-7392",
publisher = "NATURE PUBLISHING GROUP",
number = "11",

}

RIS

TY - JOUR

T1 - Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure

AU - Dirkx, Ellen

AU - Gladka, Monika M

AU - Philippen, Leonne E

AU - Armand, Anne-Sophie

AU - Kinet, Virginie

AU - Leptidis, Stefanos

AU - El Azzouzi, Hamid

AU - Salic, Kanita

AU - Bourajjaj, Meriem

AU - da Silva, Gustavo J J

AU - Olieslagers, Servé

AU - van der Nagel, Roel

AU - de Weger, Roel

AU - Bitsch, Nicole

AU - Kisters, Natasja

AU - Seyen, Sandrine

AU - Morikawa, Yuka

AU - Chanoine, Christophe

AU - Heymans, Stephane

AU - Volders, Paul G A

AU - Thum, Thomas

AU - Dimmeler, Stefanie

AU - Cserjesi, Peter

AU - Eschenhagen, Thomas

AU - da Costa Martins, Paula A

AU - De Windt, Leon J

PY - 2013/11/1

Y1 - 2013/11/1

N2 - Although aberrant reactivation of embryonic gene programs is intricately linked to pathological heart disease, the transcription factors driving these gene programs remain ill-defined. Here we report that increased calcineurin/Nfat signalling and decreased miR-25 expression integrate to re-express the basic helix-loop-helix (bHLH) transcription factor dHAND (also known as Hand2) in the diseased human and mouse myocardium. In line, mutant mice overexpressing Hand2 in otherwise healthy heart muscle cells developed a phenotype of pathological hypertrophy. Conversely, conditional gene-targeted Hand2 mice demonstrated a marked resistance to pressure-overload-induced hypertrophy, fibrosis, ventricular dysfunction and induction of a fetal gene program. Furthermore, in vivo inhibition of miR-25 by a specific antagomir evoked spontaneous cardiac dysfunction and sensitized the murine myocardium to heart failure in a Hand2-dependent manner. Our results reveal that signalling cascades integrate with microRNAs to induce the expression of the bHLH transcription factor Hand2 in the postnatal mammalian myocardium with impact on embryonic gene programs in heart failure.

AB - Although aberrant reactivation of embryonic gene programs is intricately linked to pathological heart disease, the transcription factors driving these gene programs remain ill-defined. Here we report that increased calcineurin/Nfat signalling and decreased miR-25 expression integrate to re-express the basic helix-loop-helix (bHLH) transcription factor dHAND (also known as Hand2) in the diseased human and mouse myocardium. In line, mutant mice overexpressing Hand2 in otherwise healthy heart muscle cells developed a phenotype of pathological hypertrophy. Conversely, conditional gene-targeted Hand2 mice demonstrated a marked resistance to pressure-overload-induced hypertrophy, fibrosis, ventricular dysfunction and induction of a fetal gene program. Furthermore, in vivo inhibition of miR-25 by a specific antagomir evoked spontaneous cardiac dysfunction and sensitized the murine myocardium to heart failure in a Hand2-dependent manner. Our results reveal that signalling cascades integrate with microRNAs to induce the expression of the bHLH transcription factor Hand2 in the postnatal mammalian myocardium with impact on embryonic gene programs in heart failure.

KW - Animals

KW - Base Sequence

KW - Basic Helix-Loop-Helix Transcription Factors

KW - Gene Expression Profiling

KW - Gene Silencing

KW - Heart Failure

KW - Humans

KW - Mice

KW - Mice, Knockout

KW - MicroRNAs

KW - NFATC Transcription Factors

KW - RNA Processing, Post-Transcriptional

KW - Sequence Homology, Nucleic Acid

KW - Transcription, Genetic

U2 - 10.1038/ncb2866

DO - 10.1038/ncb2866

M3 - SCORING: Journal article

C2 - 24161931

VL - 15

SP - 1282

EP - 1293

JO - NAT CELL BIOL

JF - NAT CELL BIOL

SN - 1465-7392

IS - 11

ER -