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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月29日

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  • Jasmin Bahr,
  • Gereon Poschmann,
  • Andreas Jungmann,
  • Martin Busch,
  • Zhaoping Ding,
  • Jens Vogt,
  • Ria Zalfen,
  • Julia Steinhausen,
  • Arlen Aurora Euan Martínez,
  • Thorsten Wachtmeister,
  • Daniel Rickert,
  • Tobias Lautwein,
  • Christina Alter,
  • Junedh M. Amrute,
  • Kory J. Lavine,
  • Karl Köhrer,
  • Bodo Levkau,
  • Patrick Most,
  • Kai Stühler,
  • Julia Hesse,
  • Jürgen Schrader

摘要

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.