title: Proteomic characterization of epicardial-myocardial signaling reveals novel regulatory networks including a role for NF-κB in epicardial EMT.
abstract: Signaling between the epicardium and underlying myocardium is crucial for proper heart development. 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-cultures. The 150-protein secretome dataset established 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 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 cardiac 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.
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Yanyang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pediatrics, The Feinberg School of Medicine, Northwestern University, Stanley Manne Children's Research Institute, Chicago, Illinois, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Urban
authors.affiliation: Department of Pediatrics, The Feinberg School of Medicine, Northwestern University, Stanley Manne Children's Research Institute, Chicago, Illinois, United States of America.
authors.forename: Devin
authors.initials: D
authors.lastname: Midura
authors.affiliation: Department of Pediatrics, The Feinberg School of Medicine, Northwestern University, Stanley Manne Children's Research Institute, Chicago, Illinois, United States of America.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Simon
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Q Tian
authors.initials: QT
authors.lastname: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002645:Chickens / Q000235:genetics / Q000254:growth & development; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics*; D010496:Pericardium / Q000196:embryology / Q000378:metabolism*; D040901:Proteomics; D012038:Regeneration / Q000235:genetics; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B