MBNL1 Regulates Isoproterenol-induced Myocardial Remodelling in Vitro and in Vivo

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2020 Dec 9

PMID 33295096

Citations 4

Authors

Yao Xu

Chen Liang

Ying Luo

Tongcun Zhang

Affiliations

Soon will be listed here.

Abstract

Myocardial remodelling is a common phenomenon in cardiovascular diseases, which threaten human health and the quality of life. Due to the lack of effective early diagnosis and treatment methods, the molecular mechanism of myocardial remodelling should be explored in depth. In this study, we observed the high expression of MBNL1 in cardiac tissue and peripheral blood of an isoproterenol (ISO)-induced cardiac hypertrophy mouse model. MBNL1 promoted ISO-induced cardiac hypertrophy and fibrosis by stabilizing Myocardin mRNA in vivo and in vitro. Meanwhile, an increase in MBNL1 may induce the apoptosis of cardiomyocytes treated with ISO via TNF-α signalling. Interestingly, MBNL1 can be activated by p300 in cardiomyocytes treated with ISO. At last, Myocardin can reverse activate the expression of MBNL1. These results suggest that MBNL1 may be a potential target for the early diagnosis and clinical treatment of myocardial remodelling.

Citing Articles

Functions of the Muscleblind-like protein family and their role in disease.

Zhou H, Xu J, Pan L Cell Commun Signal. 2025; 23(1):97.

PMID: 39966885 PMC: 11837677. DOI: 10.1186/s12964-025-02102-5.

Isoproterenol mechanisms in inducing myocardial fibrosis and its application as an experimental model for the evaluation of therapeutic potential of phytochemicals and pharmaceuticals.

Bader Eddin L, Nagoor Meeran M, Jha N, Goyal S, Ojha S Animal Model Exp Med. 2024; 8(1):67-91.

PMID: 39690876 PMC: 11798751. DOI: 10.1002/ame2.12496.

A Novel Circ_Arf3/miR-452-5p/Mbnl1 Axis Regulates Proliferation and Expression of Fibrosis-Related Proteins of Mouse Mesangial Cells Under High Glucose.

Wang Q, Zhu Y, Dong Q, Zhang L, Zhang W Diabetes Metab Syndr Obes. 2023; 16:2105-2116.

PMID: 37457110 PMC: 10349572. DOI: 10.2147/DMSO.S400530.

Myocardin regulates exon usage in smooth muscle cells through induction of splicing regulatory factors.

Liu L, Kryvokhyzha D, Rippe C, Jacob A, Borreguero-Munoz A, Stenkula K Cell Mol Life Sci. 2022; 79(8):459.

PMID: 35913515 PMC: 9343278. DOI: 10.1007/s00018-022-04497-7.

Loss of muscleblind splicing factor shortens Caenorhabditis elegans lifespan by reducing the activity of p38 MAPK/PMK-1 and transcription factors ATF-7 and Nrf/SKN-1.

Matilainen O, Ribeiro A, Verbeeren J, Cetinbas M, Sood H, Sadreyev R Genetics. 2021; 219(2).

PMID: 34849877 PMC: 8633093. DOI: 10.1093/genetics/iyab114.

References

Trembley M, Quijada P, Agullo-Pascual E, Tylock K, Colpan M, Dirkx Jr R . Mechanosensitive Gene Regulation by Myocardin-Related Transcription Factors Is Required for Cardiomyocyte Integrity in Load-Induced Ventricular Hypertrophy. Circulation. 2018; 138(17):1864-1878. PMC: 6202206. DOI: 10.1161/CIRCULATIONAHA.117.031788. View

Wang Y, Wang Y, Luo M, Wu H, Kong L, Xin Y . Novel curcumin analog C66 prevents diabetic nephropathy via JNK pathway with the involvement of p300/CBP-mediated histone acetylation. Biochim Biophys Acta. 2014; 1852(1):34-46. PMC: 4369325. DOI: 10.1016/j.bbadis.2014.11.006. View

Brauch K, Karst M, Herron K, de Andrade M, Pellikka P, Rodeheffer R . Mutations in ribonucleic acid binding protein gene cause familial dilated cardiomyopathy. J Am Coll Cardiol. 2009; 54(10):930-41. PMC: 2782634. DOI: 10.1016/j.jacc.2009.05.038. View

Kafasla P, Skliris A, Kontoyiannis D . Post-transcriptional coordination of immunological responses by RNA-binding proteins. Nat Immunol. 2014; 15(6):492-502. DOI: 10.1038/ni.2884. View

Freyermuth F, Rau F, Kokunai Y, Linke T, Sellier C, Nakamori M . Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy. Nat Commun. 2016; 7:11067. PMC: 4831019. DOI: 10.1038/ncomms11067. View

Wang D, Passier R, Liu Z, Shin C, Wang Z, Li S . Regulation of cardiac growth and development by SRF and its cofactors. Cold Spring Harb Symp Quant Biol. 2003; 67:97-105. DOI: 10.1101/sqb.2002.67.97. View

Han P, Li W, Lin C, Yang J, Shang C, Nuernberg S . A long noncoding RNA protects the heart from pathological hypertrophy. Nature. 2014; 514(7520):102-106. PMC: 4184960. DOI: 10.1038/nature13596. View

Xu Y, Liang C, Luo Y, Zhang T . MBNL1 regulates isoproterenol-induced myocardial remodelling in vitro and in vivo. J Cell Mol Med. 2020; 25(2):1100-1115. PMC: 7812249. DOI: 10.1111/jcmm.16177. View

Zhang L, Yang Z, Trottier J, Barbier O, Wang L . Long noncoding RNA MEG3 induces cholestatic liver injury by interaction with PTBP1 to facilitate shp mRNA decay. Hepatology. 2016; 65(2):604-615. PMC: 5258819. DOI: 10.1002/hep.28882. View

10.

Sahoo S, Meijles D, Al Ghouleh I, Tandon M, Cifuentes-Pagano E, Sembrat J . MEF2C-MYOCD and Leiomodin1 Suppression by miRNA-214 Promotes Smooth Muscle Cell Phenotype Switching in Pulmonary Arterial Hypertension. PLoS One. 2016; 11(5):e0153780. PMC: 4856285. DOI: 10.1371/journal.pone.0153780. View

11.

Mughal W, Martens M, Field J, Chapman D, Huang J, Rattan S . Myocardin regulates mitochondrial calcium homeostasis and prevents permeability transition. Cell Death Differ. 2018; 25(10):1732-1748. PMC: 6180099. DOI: 10.1038/s41418-018-0073-z. View

12.

Shirazi L, Bissett J, Romeo F, Mehta J . Role of Inflammation in Heart Failure. Curr Atheroscler Rep. 2017; 19(6):27. DOI: 10.1007/s11883-017-0660-3. View

13.

Wang D, Chang P, Wang Z, Sutherland L, Richardson J, Small E . Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor. Cell. 2001; 105(7):851-62. DOI: 10.1016/s0092-8674(01)00404-4. View

14.

Frey N, Katus H, Olson E, Hill J . Hypertrophy of the heart: a new therapeutic target?. Circulation. 2004; 109(13):1580-9. DOI: 10.1161/01.CIR.0000120390.68287.BB. View

15.

Sheng J, Jin J . Gene regulation, alternative splicing, and posttranslational modification of troponin subunits in cardiac development and adaptation: a focused review. Front Physiol. 2014; 5:165. PMC: 4012202. DOI: 10.3389/fphys.2014.00165. View

16.

Cokkinos D, Pantos C . Myocardial remodeling, an overview. Heart Fail Rev. 2010; 16(1):1-4. DOI: 10.1007/s10741-010-9192-4. View

17.

Hulsmans M, Sam F, Nahrendorf M . Monocyte and macrophage contributions to cardiac remodeling. J Mol Cell Cardiol. 2015; 93:149-55. PMC: 4846552. DOI: 10.1016/j.yjmcc.2015.11.015. View

18.

Davis J, Salomonis N, Ghearing N, Lin S, Kwong J, Mohan A . MBNL1-mediated regulation of differentiation RNAs promotes myofibroblast transformation and the fibrotic response. Nat Commun. 2015; 6:10084. PMC: 4703843. DOI: 10.1038/ncomms10084. View

19.

Bao D, Lu D, Liu N, Dong W, Lu Y, Qin C . Tomoregulin-1 prevents cardiac hypertrophy after pressure overload in mice by inhibiting TAK1-JNK pathways. Dis Model Mech. 2015; 8(8):795-804. PMC: 4527297. DOI: 10.1242/dmm.021303. View

20.

Lionetti V, Aquaro G, Simioniuc A, Di Cristofano C, Forini F, Cecchetti F . Severe mechanical dyssynchrony causes regional hibernation-like changes in pigs with nonischemic heart failure. J Card Fail. 2009; 15(10):920-8. DOI: 10.1016/j.cardfail.2009.06.436. View