Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure
| العنوان: | Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure |
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| المؤلفون: | Peter Cserjesi, Christophe Chanoine, Leonne E Philippen, Monika M Gladka, Natasja Kisters, Roel van der Nagel, Nicole Bitsch, Kanita Salic, Paula A. da Costa Martins, Servé Olieslagers, Stefanos Leptidis, Roel A. de Weger, Hamid el Azzouzi, Leon J. De Windt, Virginie Kinet, Ellen Dirkx, Paul G.A. Volders, Sandrine R.M. Seyen, Anne-Sophie Armand, Stephane Heymans, Meriem Bourajjaj, Yuka Morikawa, Thomas Thum, Stefanie Dimmeler, Gustavo J. J. Silva, Thomas Eschenhagen |
| المساهمون: | Genetica & Celbiologie, RS: CARIM School for Cardiovascular Diseases, Promovendi CD, Cardiologie, RS: CARIM - R2.07 - Gene regulation, Ondersteunend personeel CD |
| المصدر: | Nature Cell Biology, 15(11), 1282-1293. Nature Publishing Group Nature Cell Biology |
| بيانات النشر: | Nature Publishing Group, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Transcription, Genetic, 030204 cardiovascular system & hematology, Muscle hypertrophy, Mice, 03 medical and health sciences, 0302 clinical medicine, Sequence Homology, Nucleic Acid, Basic Helix-Loop-Helix Transcription Factors, medicine, Animals, Humans, Gene silencing, Gene Silencing, RNA Processing, Post-Transcriptional, Transcription factor, 030304 developmental biology, Heart Failure, Mice, Knockout, 0303 health sciences, Base Sequence, NFATC Transcription Factors, biology, Gene Expression Profiling, NFAT, Cell Biology, medicine.disease, 3. Good health, Cell biology, Calcineurin, Gene expression profiling, MicroRNAs, Heart failure, embryonic structures, Cancer research, biology.protein, HAND2 |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1465-7392 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bf26275e0f6dd8a3f3c23a30b681952aTest https://cris.maastrichtuniversity.nl/en/publications/2b0357ea-a1da-4907-ae44-427fece68208Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bf26275e0f6dd8a3f3c23a30b681952a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14657392 |
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