Intercardiac Phosphoproteome/proteome regulation of cardiomyocyte-fibroblast signaling
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ABSTRACT: 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
INSTRUMENT(S): Q Exactive HF-X
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: David Greening
PROVIDER: MSV000092293 | MassIVE | Tue Jun 27 21:57:00 BST 2023
REPOSITORIES: MassIVE
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