Deciphering the role of wnt and rho signaling pathway in ipsc-derived arvc cardiomyocytes by in silico mathematical modeling
Parrotta EI, Procopio A, Scalise S, Esposito C, Nicoletta G, Santamaria G, De Angelis MT, Dorn T, Moretti A, Laugwitz KL, Montefusco F, Cosentino C, Cuda G (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 22
Pages Range: 1-19
Article Number: 2004
Journal Issue: 4
DOI: 10.3390/ijms22042004
Abstract
Arrhythmogenic Right Ventricular cardiomyopathy (ARVC) is an inherited cardiac muscle disease linked to genetic deficiency in components of the desmosomes. The disease is characterized by progressive fibro-fatty replacement of the right ventricle, which acts as a substrate for arrhythmias and sudden cardiac death. The molecular mechanisms underpinning ARVC are largely unknown. Here we propose a mathematical model for investigating the molecular dynamics underlying heart remodeling and the loss of cardiac myocytes identity during ARVC. Our methodology is based on three computational models: firstly, in the context of the Wnt pathway, we examined two different competition mechanisms between β-catenin and Plakoglobin (PG) and their role in the expression of adipogenic program. Secondly, we investigated the role of RhoA-ROCK pathway in ARVC pathogenesis, and thirdly we analyzed the interplay between Wnt and RhoA-ROCK pathways in the context of the ARVC phenotype. We conclude with the following remark: both Wnt/β-catenin and RhoA-ROCK pathways must be inactive for a significant increase of PPARγ expression, suggesting that a crosstalk mechanism might be responsible for mediating ARVC pathogenesis.
Involved external institutions
Magna Græcia University of Catanzaro / Università degli studi Magna Græcia di Catanzaro
Italy (IT)
Technische Universität München (TUM)
Germany (DE)
Università degli Studi di Sassari (UNISS)
Italy (IT)
Italy (IT)
Technische Universität München (TUM)
Germany (DE)
Università degli Studi di Sassari (UNISS)
Italy (IT)
How to cite
APA:
Parrotta, E.I., Procopio, A., Scalise, S., Esposito, C., Nicoletta, G., Santamaria, G.,... Cuda, G. (2021). Deciphering the role of wnt and rho signaling pathway in ipsc-derived arvc cardiomyocytes by in silico mathematical modeling. International Journal of Molecular Sciences, 22(4), 1-19. https://doi.org/10.3390/ijms22042004
MLA:
Parrotta, Elvira Immacolata, et al. "Deciphering the role of wnt and rho signaling pathway in ipsc-derived arvc cardiomyocytes by in silico mathematical modeling." International Journal of Molecular Sciences 22.4 (2021): 1-19.
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