A secretome atlas of cardiac fibroblasts from healthy and infarcted mouse hearts
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.
Authors
- Junedh Amrute (ORCID: https://orcid.org/0000-0002-6851-0168)
- Kory J. Lavine (ORCID: https://orcid.org/0000-0003-1948-9945)
- Ria Zalfen
- Jasmin Bahr (ORCID: https://orcid.org/0000-0002-0178-2804)
- Zhaoping Ding (ORCID: https://orcid.org/0000-0002-4242-2450)
- Christina Alter (ORCID: https://orcid.org/0009-0007-8608-2033)
- Patrick Most (ORCID: https://orcid.org/0000-0001-7889-7063)
- Jens Vogt (ORCID: https://orcid.org/0009-0000-0789-3751)
- Julia Hesse (ORCID: https://orcid.org/0000-0001-8555-259X)
- Jürgen Schrader (ORCID: https://orcid.org/0000-0002-7742-2768)
- Andreas Jungmann
- Karl Köhrer (ORCID: https://orcid.org/0000-0003-3644-2022)
- Thorsten Wachtmeister (ORCID: https://orcid.org/0000-0002-6760-2458)
- Julia Steinhausen
- Kai Stühler (ORCID: https://orcid.org/0000-0002-3111-9368)
- Gereon Poschmann (ORCID: https://orcid.org/0000-0003-2448-0611)
- Bodo Levkau (ORCID: https://orcid.org/0000-0002-0005-125X)
- Tobias Lautwein (ORCID: https://orcid.org/0000-0002-3872-3613)
- Martin Busch (ORCID: https://orcid.org/0000-0002-2717-7063)
- Daniel Rickert
Institutions
- Washington University in St. Louis (US)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- Düsseldorf University Hospital (DE)
- Heinrich Heine University Düsseldorf (DE)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-04-29
- DOI
- https://doi.org/10.1038/s42003-025-08083-y
- Citations
- 7
- Primary Topic
- Peptidase Inhibition and Analysis
- Type
- article
- Field-Weighted Citation Impact
- 7.32
Funders
- Deutsche Forschungsgemeinschaft