Sassi, Y;
Avramopoulos, P;
Ramanujam, D;
Grueter, L;
Werfel, S;
Giosele, S;
Brunner, A-D;
... Engelhardt, S; + view all
(2017)
Cardiac myocyte miR-29 promotes pathological remodeling of the heart by activating Wnt signaling.
Nature Communications
, 8
, Article 1614. 10.1038/s41467-017-01737-4.
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Abstract
Chronic cardiac stress induces pathologic hypertrophy and fibrosis of the myocardium. The microRNA-29 (miR-29) family has been found to prevent excess collagen expression in various organs, particularly through its function in fibroblasts. Here, we show that miR-29 promotes pathologic hypertrophy of cardiac myocytes and overall cardiac dysfunction. In a mouse model of cardiac pressure overload, global genetic deletion of miR-29 or antimiR-29 infusion prevents cardiac hypertrophy and fibrosis and improves cardiac function. Targeted deletion of miR-29 in cardiac myocytes in vivo also prevents cardiac hypertrophy and fibrosis, indicating that the function of miR-29 in cardiac myocytes dominates over that in non-myocyte cell types. Mechanistically, we found cardiac myocyte miR-29 to de-repress Wnt signaling by directly targeting four pathway factors. Our data suggests that, cell- or tissue-specific antimiR-29 delivery may have therapeutic value for pathological cardiac remodeling and fibrosis.
| Type: | Article |
|---|---|
| Title: | Cardiac myocyte miR-29 promotes pathological remodeling of the heart by activating Wnt signaling |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-017-01737-4 |
| Publisher version: | http://doi.org/10.1038/s41467-017-01737-4 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, IN-VIVO, ANEURYSM DEVELOPMENT, COLLAGEN EXPRESSION, PULMONARY-FIBROSIS, CATENIN PATHWAY, RENAL FIBROSIS, LIVER FIBROSIS, GROWTH-FACTOR, MICRORNAS, HYPERTROPHY |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UK Dementia Research Institute HQ |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10039884 |
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