Mapping signalling perturbations in myocardial fibrosis via the integrative phosphoproteomic profiling of tissue from diverse sources



Kuzmanov, Uros, Wang, Erika Yan, Vanderlaan, Rachel, Kim, Da Hye, Lee, Shin-Haw, Hadipour-Lakmehsari, Sina, Guo, Hongbo, Zhao, Yimu, McFadden, Meghan, Sharma, Parveen ORCID: 0000-0002-5534-2417
et al (show 4 more authors) (2020) Mapping signalling perturbations in myocardial fibrosis via the integrative phosphoproteomic profiling of tissue from diverse sources. Nature Biomedical Engineering, 4 (9). 889 - 900.

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Abstract

Study of the molecular basis of myocardial fibrosis is hampered by limited access to tissues from human patients and by confounding variables associated with sample accessibility, collection, processing and storage. Here, we report an integrative strategy based on mass spectrometry for the phosphoproteomic profiling of normal and fibrotic cardiac tissue obtained from surgical explants from patients with hypertrophic cardiomyopathy, from a transaortic-constriction mouse model of cardiac hypertrophy and fibrosis, and from a heart-on-a-chip model of cardiac fibrosis. We used the integrative approach to map the relative abundance of thousands of proteins, phosphoproteins and phosphorylation sites specific to each tissue source, to identify key signalling pathways driving fibrosis and to screen for anti-fibrotic compounds targeting glycogen synthase kinase 3, which has a consistent role as a key mediator of fibrosis in all three types of tissue specimen. The integrative disease-modelling strategy may reveal new insights into mechanisms of cardiac disease and serve as a test bed for drug screening.

Item Type: Article
Uncontrolled Keywords: Biomarkers, Cardiology, Kinases, Pathogenesis, Proteomics
Depositing User: Symplectic Admin
Date Deposited: 15 Jul 2020 10:23
Last Modified: 22 Jan 2022 10:10
DOI: 10.1038/s41551-020-0585-y
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3094092