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The long non-coding RNA NRONpromotes the development of cardiac hypertrophy in the murine heart
- Source :
- Molecular Therapy; March 2022, Vol. 30 Issue: 3 p1265-1274, 10p
- Publication Year :
- 2022
-
Abstract
- Physiological and pathological cardiovascular processes are tightly regulated by several cellular mechanisms. Non-coding RNAs, including long non-coding RNAs (lncRNAs), represent one important class of molecules involved in regulatory processes within the cell. The lncRNA non-coding repressor of NFAT(NRON) was described as a repressor of the nuclear factor of activated T cells (NFAT) in different in vitrostudies. Although the calcineurin/NFAT-signaling pathway is one of the most important pathways in pathological cardiac hypertrophy, a potential regulation of hypertrophy by NRON in vivohas remained unclear. Applying subcellular fractionation and RNA fluorescence in situhybridization (RNA-FISH), we found that, unlike what is known from T cells, in cardiomyocytes, NRONpredominantly localizes to the nucleus. Hypertrophic stimulation in neonatal mouse cardiomyocytes led to a downregulation of NRON, while NRONoverexpression led to an increase in expression of hypertrophic markers. To functionally investigate NRON in vivo, we used a mouse model of transverse aortic constriction (TAC)-induced hypertrophy and performed NRONgain- and loss-of-function experiments. Cardiomyocyte-specific NRONoverexpression in vivoexacerbated TAC-induced hypertrophy, whereas cardiomyocyte-specific NRONdeletion attenuated cardiac hypertrophy in mice. Heart weight, cardiomyocyte cell size, hypertrophic marker gene expression, and left ventricular mass showed a NRON-dependent regulation upon TAC-induced hypertrophy. In line with this, transcriptome profiling revealed an enrichment of anti-hypertrophic signaling pathways upon NRON-knockout during TAC-induced hypertrophy. This set of data refutes the hypothesized anti-hypertrophic role of NRONderived from in vitrostudies in non-cardiac cells and suggests a novel regulatory function of NRONin the heart in vivo.
Details
- Language :
- English
- ISSN :
- 15250016 and 15250024
- Volume :
- 30
- Issue :
- 3
- Database :
- Supplemental Index
- Journal :
- Molecular Therapy
- Publication Type :
- Periodical
- Accession number :
- ejs58370037
- Full Text :
- https://doi.org/10.1016/j.ymthe.2021.11.018