MassIVE MSV000092293

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intercardiac Phosphoproteome/proteome regulation of cardiomyocyte-fibroblast signaling

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Description

Secretome-mediated signaling from human iPSC-derived cardiomyocytes (TGF-beta induced dysfunction) to primary human cardiac fibroblasts was investigated to identify downstream regulators of fibrosis. Quantitative proteomic profiling revealed a dynamic reprogramming of fibroblast global proteome, with dysregulation of proteins implicated in extracellular matrix (ECM) remodelling, cytoskeleton organization, lysosome function, and oxidoreductase- and kinase activity. Protein modification-focused processing analyses of mass spectrometry proteome data further highlight phospho-proteome alterations in pro-fibrotic pathways regulated by kinases (CK2, CDK1, CDK2, MAPK1, PRKACA, PRKG1). We verified upregulated casein kinase 2 (CK2) substrate levels in secretome-treated fibroblasts, and pharmacological inhibition of CK2 using Tetrabromobenzotriazole significantly abrogated reactive oxygen species levels and activation state [doi:10.25345/C53N20Q62] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: fibroblast, intercellular signaling, phosphoproteomics

Contact

Principal Investigators:
(in alphabetical order) 		David Greening, Baker Heart & Diabetes Institute, Australia
Submitting User: dwgree

Publications

Claridge B, Rai A, Lees JG, Fang H, Lim SY, Greening DW.
Cardiomyocyte intercellular signalling increases oxidative stress and reprograms the global- and phospho-proteome of cardiac fibroblasts.
J Extracell Biol. 2023 Dec;2(12):e125. Epub 2023 Nov 30.

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