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Updated: Jun 25, 2026
Induction of Endothelial Differentiation in Cardiac Progenitor Cells Under Low Serum Conditions
Published on: January 7, 2019
Signals through glycoprotein 130 regulate the endothelial differentiation of cardiac stem cells
Tomomi Mohri1, Yasushi Fujio, Masanori Obana
1Department of Clinical Pharmacology and Pharmacogenomics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita City, Osaka, Japan.
Insights
Proinflammatory cytokines interleukin-11 (IL-11) and cardiotrophin-1 (CT-1) promote cardiac Sca-1+ cell endothelial differentiation via the gp130/STAT3 pathway. This pathway is crucial for regulating stem cell differentiation in the heart.
Area of Science:
- Cardiovascular biology
- Stem cell research
- Molecular signaling
Background:
- Cardiac Sca-1+ cells are recognized for their multipotent stem cell characteristics.
- Understanding the regulation of cardiac stem cell differentiation is vital for regenerative medicine.
Purpose of the Study:
- To investigate the impact of proinflammatory cytokines on the endothelial differentiation of cardiac Sca-1+ cells.
- To elucidate the molecular mechanisms governing this differentiation process.
Main Methods:
- Cardiac Sca-1+ cells were exposed to various proinflammatory cytokines, including IL-11 and CT-1.
- Gene expression (RT-PCR), protein analysis (immunoblotting), and STAT3 inhibition were employed.
- Analysis of postinfarct myocardium for relevant gene and cell markers.
Main Results:
- Interleukin-11 (IL-11) and cardiotrophin-1 (CT-1) induced endothelial-specific genes in cardiac Sca-1+ cells via the glycoprotein 130 (gp130) receptor.
- These cytokines activated Signal Transducer and Activator of Transcription 3 (STAT3) phosphorylation.
- Inhibition of STAT3 blocked IL-11 and CT-1-induced endothelial differentiation.
- Upregulation of IL-11 and Sca-1+/VE-cadherin+ cells was observed in postinfarct hearts.
Conclusions:
- The gp130/STAT3 signaling pathway is a critical regulator of cardiac Sca-1+ cell endothelial differentiation.
- These findings highlight a potential mechanism for cardiac repair involving stem cell differentiation.
Objective:
Cardiac Sca-1+ cells were originally identified as multipotent stem cells. To address the regulation of their differentiation, we investigated the effects of the proinflammatory cytokines on their endothelial differentiation.
Methods And Results:
We examined the effects of the proinflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, IL-11, and cardiotrophin-1 (CT-1) on the cardiac Sca-1+ cell differentiation. IL-11 and CT-1, whose receptor systems use glycoprotein 130 (gp130), induced endothelial-specific genes in Sca-1+ cells, but not TNF-alpha, IL-1beta, or IL-6, analyzed by RT-PCR and by immunocytochemistry. Immnunoblot analyses showed that IL-11 and CT-1 activated signal transducer and activator of transcription 3 (STAT3), a downstream target of gp130, but not other cytokines. Though IL-6 receptor is not endogenously expressed in Sca-1+ cells, IL-6 exhibited the activity to induce the endothelial markers in the presence of soluble IL-6 receptor, an agonistic receptor, associated with STAT3 phosphorylation. Moreover, the inhibition of STAT3, by its dominant-negative form or siRNA, suppressed the induction of endothelial specific genes by IL-11 and CT-1. Finally, LIF and IL-11 transcripts were upregulated in postinfarct myocardium, accompanied by the induction of Sca-1+/VE-cadherin+ cells.
Conclusions:
Gp130/STAT3 pathway plays critical roles in the regulation of endothelial differentiation of cardiac Sca-1+ cells.
