Proteomics

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Intercardiac Phosphoproteome/proteome regulation of cardiomyocyte-fibroblast signaling

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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Publications

Cardiomyocyte intercellular signalling increases oxidative stress and reprograms the global- and phospho-proteome of cardiac fibroblasts.

Claridge Bethany B   Rai Alin A   Lees Jarmon G JG   Fang Haoyun H   Lim Shiang Y SY   Greening David W DW  

Journal of extracellular biology 20231130 12

Pathological reprogramming of cardiomyocyte and fibroblast proteome landscapes drive the initiation and progression of cardiac fibrosis. Although the secretome of dysfunctional cardiomyocytes is emerging as an important driver of pathological fibroblast reprogramming, our understanding of the downstream molecular players remains limited. Here, we show that cardiac fibroblast activation (αSMA<sup>+</sup>) and oxidative stress mediated by the secretome of TGFβ-stimulated cardiomyocytes is associat  ...[more]

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