Cardiomyocytes regulate cardiac fibroblast activation and oxidative stress via CK2 signaling

ABSTRACT: Secretome-mediated signaling from human iPSC-derived cardiomyocytes (TGFβ 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 various 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 TBB (4,5,6,7-Tetrabromobenzotriazole) significantly abrogated reactive oxygen species’ levels and activation state (SMA+).

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Heart, Fibroblast

DISEASE(S): Cardiovascular System Disease

SUBMITTER: david greening  

LAB HEAD: David Greening

PROVIDER: PXD038854 | Pride | 2025-02-11

REPOSITORIES: pride