thymosin-beta(4) and Cardiomegaly

Thymosin beta-4 (Tβ4) is an actin sequestering protein and is furthermore involved in diverse biological processes including cell proliferation, differentiation, wound healing, stem- or progenitor cell differentiation, and modulates inflammatory mediators. Tβ4 also attenuates fibrosis. However, the role of Tβ4 in cardiomyocytes hypertrophy is unknown.. In this review, we will discuss the role of Tβ4 in cardiac remodeling that specifically includes cardiac hypertrophy and fibrosis only. Our review will further cover a new signaling pathway, the wingless and integrated-1 (Wnt) pathway in cardiac remodeling. In rat neonatal and adult cardiomyocytes stimulated with angiotensin II (Ang II), we showed that Tβ4 has the ability to reduce cell sizes, attenuate hypertrophy marker genes expression, along with a panel of WNT-associated gene expressions induced by Ang II. Selected target gene WNT1-inducible-signaling pathway protein 1 (WISP-1) was identified by Tβ4. Data further confirmed that WISP-1 overexpression promoted cardiomyocytes growth and was reversed by Tβ4 pretreatment.. Our data suggested that Tβ4 protects cardiomyocytes from hypertrophic response by targeting WISP-1. The new role of Tβ4 in cardiac hypertrophy advances our understanding, and the mechanism of action of Tβ4 may provide a solid foundation for the treatment of cardiac disease.

Topics: Angiotensin II; Animals; Animals, Newborn; Cardiomegaly; Cell Differentiation; Cell Proliferation; Humans; Myocytes, Cardiac; Rats; Signal Transduction; Thymosin

Thymosin beta-4 (Tβ4) is a ubiquitous protein with many properties relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory mediators. However, the role of Tβ4 in cardiomyocyte hypertrophy is currently unknown. The purpose of this study was to determine the cardio-protective effect of Tβ4 in angiotensin II (Ang II)-induced cardiomyocyte growth. Neonatal rat ventricular cardiomyocytes (NRVM) were pretreated with Tβ4 followed by Ang II stimulation. Cell size, hypertrophy marker gene expression and Wnt signaling components, β-catenin, and Wnt-induced secreted protein-1 (WISP-1) were evaluated by quantitative real-time PCR, Western blotting and fluorescent microscopy. Pre-treatment of Tβ4 resulted in reduction of cell size, hypertrophy marker genes and Wnt-associated gene expression, and protein levels; induced by Ang II in cardiomyocyte. WISP-1 was overexpressed in NRVM and, the effect of Tβ4 in Ang II-induced cardiomyocyte growth was evaluated. WISP-1 overexpression promoted cardiomyocytes growth and was reversed by pretreatment with Tβ4. This is the first report which demonstrates that Tβ4 targets Wnt/WISP-1 to protect Ang II-induced cardiomyocyte growth. J. Cell. Physiol. 231: 1737-1744, 2016. © 2015 Wiley Periodicals, Inc.

Topics: Active Transport, Cell Nucleus; Angiotensin II; Animals; Animals, Newborn; beta Catenin; Cardiomegaly; CCN Intercellular Signaling Proteins; Cell Size; Cells, Cultured; Gene Expression Regulation; Myocytes, Cardiac; Proto-Oncogene Proteins; Rats, Sprague-Dawley; Thymosin; Transfection; Wnt Signaling Pathway