Thymosin β4 Prevents Angiotensin II-Induced Cardiomyocyte Growth by Regulating Wnt/WISP Signaling

Area of Science:

• Cardiology
• Molecular Biology
• Cell Biology

Background:

• Thymosin beta-4 (Tβ4) is a protein involved in cell proliferation and differentiation, promoting wound healing and modulating inflammation.
• The specific role of Tβ4 in cardiomyocyte hypertrophy, a key factor in heart disease, was previously unknown.

Purpose of the Study:

• To investigate the potential cardio-protective effects of Tβ4 against angiotensin II (Ang II)-induced cardiomyocyte growth.
• To elucidate the molecular mechanisms underlying Tβ4's action in cardiomyocytes.

Main Methods:

• Neonatal rat ventricular cardiomyocytes (NRVM) were pretreated with Tβ4 before Ang II stimulation.
• Quantitative real-time PCR, Western blotting, and fluorescent microscopy were used to assess cell size, gene expression, and protein levels.
• Wnt signaling components, including β-catenin and Wnt-induced secreted protein-1 (WISP-1), were specifically evaluated.

Main Results:

• Tβ4 pretreatment significantly reduced Ang II-induced cardiomyocyte size and hypertrophy marker gene expression.
• Tβ4 decreased Wnt signaling components, including β-catenin and WISP-1, at both gene and protein levels.
• Overexpression of WISP-1 promoted cardiomyocyte growth, an effect that was reversed by Tβ4 pretreatment.

Conclusions:

• This study demonstrates that Tβ4 exerts a cardio-protective effect against Ang II-induced cardiomyocyte hypertrophy.
• Tβ4 acts by targeting the Wnt/WISP-1 signaling pathway to inhibit cardiomyocyte growth.
• These findings identify Tβ4 as a potential therapeutic target for preventing or treating cardiac hypertrophy.