Proteomic characterization of epicardialmyocardial signaling reveals novel regulatory networks including a role for NF-κB in epicardial EMT

Yanyang Li, Alexander Urban, Devin Midura, Hans Georg Simon, Q. Tian Wang

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 EPDCheart 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.

Original languageEnglish (US)
Article numbere0174563
JournalPloS one
Volume12
Issue number3
DOIs
StatePublished - Mar 2017

ASJC Scopus subject areas

  • General

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