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  2. A secretome atlas of cardiac fibroblasts from healthy and infarcted mouse hearts

A secretome atlas of cardiac fibroblasts from healthy and infarcted mouse hearts

  • Commun Biol. 2025 Apr 29;8(1):675. doi: 10.1038/s42003-025-08083-y.
Jasmin Bahr 1 Gereon Poschmann 2 Andreas Jungmann 3 Martin Busch 3 Zhaoping Ding 1 Jens Vogt 4 Ria Zalfen 1 Julia Steinhausen 1 Arlen Aurora Euan Martínez 1 Thorsten Wachtmeister 5 Daniel Rickert 5 Tobias Lautwein 5 Christina Alter 1 Junedh M Amrute 6 Kory J Lavine 6 Karl Köhrer 5 Bodo Levkau 4 7 Patrick Most 3 Kai Stühler 2 8 Julia Hesse 9 10 Jürgen Schrader 11 12
Affiliations

Affiliations

  • 1 Department of Molecular Cardiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • 2 Institute for Molecular Medicine, Proteome Research, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • 3 Division of Molecular and Translational Cardiology, Department of Internal Medicine III, Heidelberg University Hospital, Heidelberg, Germany.
  • 4 Institute of Molecular Medicine III, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • 5 Genomics & Transcriptomics Laboratory, Biological and Medical Research Centre (BMFZ), Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • 6 Center for Cardiovascular Research, Department of Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, USA.
  • 7 CARID, Cardiovascular Research Institute Düsseldorf, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • 8 Molecular Proteomics Laboratory, Biological and Medical Research Centre (BMFZ), Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • 9 Department of Molecular Cardiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. julia.hesse@uni-duesseldorf.de.
  • 10 CARID, Cardiovascular Research Institute Düsseldorf, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. julia.hesse@uni-duesseldorf.de.
  • 11 Department of Molecular Cardiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. schrader@uni-duesseldorf.de.
  • 12 CARID, Cardiovascular Research Institute Düsseldorf, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. schrader@uni-duesseldorf.de.
Abstract

Cardiac fibroblasts (CF) are key players after myocardial infarction (MI), but their signaling is only incompletely understood. Here we report a first secretome atlas of CF in control (cCF) and post-MI mouse hearts (miCF), combining a rapid Cell Isolation technique with SILAC and click chemistry. In CF, numerous paracrine factors involved in immune homeostasis are identified. Comparing secretome, transcriptome (SLAMseq), and cellular proteome disclose protein turnover. In miCF at day 5 post-MI, significantly upregulated proteins include SLIT2, FN1, and CRLF1 in mouse and human samples. Comparing the miCF secretome at days 3 and 5 post-MI reveals the dynamic nature of protein secretion. Specific in-vivo labeling of miCF proteins via biotin Ligase TurboID using the POSTN promotor mirrors the in-vitro data. In summary, we identify numerous paracrine factors specifically secreted from CF in mice and humans. This secretome atlas may lead to new biomarkers and/or therapeutic targets for the activated CF.

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