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

TY - JOUR

T1 - No effect of thymosin beta-4 on the expression of the transcription factor Islet-1 in the adult murine heart

AU - Weinberger, Florian

AU - Nicol, Philipp

AU - Starbatty, Jutta

AU - Stubbendorff, Mandy

AU - Becher, Peter M

AU - Schrepfer, Sonja

AU - Eschenhagen, Thomas

N1 - © 2018 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

PY - 2018/6/3

Y1 - 2018/6/3

N2 - 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.

AB - 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.

KW - Animals

KW - Cells, Cultured

KW - Disease Models, Animal

KW - Gene Expression Regulation

KW - Heart Ventricles

KW - LIM-Homeodomain Proteins

KW - Mice

KW - Mice, Transgenic

KW - Myocardial Infarction

KW - Sinoatrial Node

KW - Stem Cells

KW - Thymosin

KW - Transcription Factors

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/prp2.407

DO - 10.1002/prp2.407

M3 - SCORING: Journal article

C2 - 29864245

VL - 6

SP - e00407

JO - PHARMACOL RES PERSPE

JF - PHARMACOL RES PERSPE

SN - 2052-1707

IS - 3

ER -