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Proteomic Characterization of Epicardial‐Myocardial Signaling Reveals Novel Regulatory Networks Including a Role for NF‐κB in Epicardial EMT
Author(s) -
Li Yanyang,
Urban Alexander,
Midura Devin,
Simon HansGeorg,
Wang Q. Tian
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb638
Subject(s) - crosstalk , signal transduction , heart development , biology , regeneration (biology) , microbiology and biotechnology , embryonic heart , epithelial–mesenchymal transition , cell signaling , computational biology , embryonic stem cell , transition (genetics) , genetics , gene , physics , optics
Reciprocal signaling between the epicardium and underlying myocardium not only is essential for heart development, but also plays a critical role during heart regeneration in regeneration‐competent vertebrates. The complex molecular interactions and regulatory networks involved in this communication are not well understood. In this study, we integrated mass spectrometry with bioinformatics to systematically characterize the secretome of embryonic chicken EPDC‐heart explant (EHE) co‐culture. The 150‐protein secretome dataset established here greatly expands the knowledge base of the molecular players involved in epicardial‐myocardial signaling. We identified proteins and pathways that are implicated in epicardial‐myocardial signaling for the first time, as well as new components of pathways that are known to regulate the crosstalk between epicardium and myocardium. The large size of the dataset enabled bioinformatics analysis to deduce functional networks for the regulation of specific biological processes and predicted signal transduction nodes within the networks. We performed functional analysis on one of the predicted nodes, NF‐κB, and demonstrate that NF‐κB activation is an essential step in TGFβ2/PDGFBB‐induced epithelial‐to‐mesenchymal transition. In summary, we have generated a global perspective of epicardial‐myocardial signaling for the first time, and our findings open exciting new avenues for investigating the molecular basis of heart development and regeneration. Support or Funding Information This work was funded by the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust.