No effect of thymosin beta‐4 on the expression of the transcription factor Islet‐1 in the adult murine heart

• Published in: Pharmacology research & perspectives Vol. 6; no. 3; pp. e00407 - n/a
• Main Authors: Weinberger, Florian, Nicol, Philipp, Starbatty, Jutta, Stubbendorff, Mandy, Becher, Peter M., Schrepfer, Sonja, Eschenhagen, Thomas
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.06.2018; John Wiley and Sons Inc
• Subjects: Animals; cardiac progenitor cells; cardiac regeneration; cardiac transcription factors; Cardiomyocytes; Cells, Cultured; Disease Models, Animal; Fibroblasts; Gene Expression Regulation; Heart attacks; Heart Ventricles - cytology; Heart Ventricles - drug effects; Heart Ventricles - metabolism; Laboratory animals; LIM-Homeodomain Proteins - genetics; LIM-Homeodomain Proteins - metabolism; Mice; Mice, Transgenic; Myocardial Infarction - genetics; Original; Ostomy; Pharmacology; Potassium; Sinoatrial Node - cytology; Sinoatrial Node - drug effects; Sinoatrial Node - metabolism; Smooth muscle; Stem Cells - cytology; Stem Cells - drug effects; Stem Cells - metabolism; Thymosin - administration & dosage; Thymosin - pharmacology; thymosin beta‐4; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; cardiac regeneration; cardiac progenitor cells; cardiac transcription factors; thymosin beta-4
• ISSN: 2052-1707; 2052-1707
• DOI: 10.1002/prp2.407

The transcription factor Islet‐1 marks a progenitor cell population of the second heart field during cardiogenesis. In the adult heart Islet‐1 expression is limited to the sinoatrial node, the ventricular outflow tract, and parasympathetic ganglia. The regenerative effect in the injured mouse ventricle of thymosin beta‐4 (TB4), a 43‐aminoacid peptide, was associated with increased Islet‐1 immunostaining, suggesting the induction of an Islet‐1‐positive progenitor state by TB4. Here we aimed to reassess this effect in a genetic model. Mice from the reporter mouse line Isl1‐nLacZ were primed with TB4 and subsequently underwent myocardial infarction. Islet‐1 expression was assessed 2, 7, and 14 days after infarction. We detected only a single Islet‐1+ cell in 8 TB4 treated and infarcted hearts which located outside of the sinoatrial node, the outflow tract or cardiac ganglia (in ~2500 sections). Two cells were identified in 5 control infarcted hearts. TB4 did not induce LacZ positivity in ventricular explants cultures of Isl1‐nLacZ mice nor did it affect the density of LacZ+ cells in explant cultures of nLacZ+ regions of the heart. In summary, we found no evidence that TB4 reactivates Islet‐1 expression in adult mouse ventricle.