HMGB1-stimulated human primary cardiac fibroblasts exert a paracrine action on human and murine cardiac stem cells

Alessandra Rossini, Antonella Zacheo, David Mocini, Pierangela Totta, Antonio Facchiano, Raffaella Castoldi, Paolo Sordini, Giulio Pompilio, Damiano Abeni, Maurizio C. Capogrossi, Antonia Germani

Research output: Contribution to journalArticlepeer-review


High Mobility Box 1 Protein (HMGB1) is a cytokine released into the extracellular space by necrotic cells and activated macrophages in response to injury. We recently demonstrated that HMGB1 administration into the mouse heart during acute myocardial infarction induces cardiac tissue regeneration by activating resident cardiac c-kit+ cells (CSCs) and significantly enhances left ventricular function. In the present study it was analyzed the hypothesis that human cardiac fibroblasts (cFbs) exposed to HMGB1 may exert a paracrine effect on mouse and human CSCs. Human cFbs expressed the HMGB1 receptor RAGE. Luminex technology and ELISA assays revealed that HMGB1 significantly enhanced VEGF, PlGF, Mip-1α, IFN-γ, GM-CSF, Il-10, Il-1β, Il-4, Il-1ra, Il-9 and TNF-α in cFbs cell culture medium. HMGB1-stimulated cFbs conditioned media induced CSC migration and proliferation. These effects were significantly higher to those obtained when HMGB1 was added directly to the culture medium. In conclusion, we provide evidence that HMGB1 may act in a paracrine manner stimulating growth factor, cytokine and chemokine release by cFbs which, in turn, modulate CSC function. Via this mechanism HMGB1 may contribute to cardiac tissue regeneration.

Original languageEnglish
Pages (from-to)683-693
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Issue number4
Publication statusPublished - Apr 2008


  • Cardiac stem cells
  • Chemokines
  • Cytokines
  • Growth factors
  • Migration
  • Paracrine action
  • Proliferation

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine


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