The role of Thymosin β4 in angiotensin II-induced cardiomyocytes growth

ABSTRACT

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

KEYWORDS:

• Thymosin β4
• cardiac hypertrophy
• Wnt signaling
• WISP1

Article Highlights

• Tβ4 is an actin sequestering protein and has shown its role in many diverse biological processes including cardiac pathologies. Tβ4 is tested for clinical trial for MI.

• This review provided evidence for new role of Tβ4 in cardiac hypertrophy.

• The Wnt signaling pathway is evolutionary conserved and regulate cardiogenesis and cardiac development. Several components of Wnt pathway have been implicated to participate in cardiac diseases including hypertrophy.

• This review identified a new candidate, the WISP1 in Ang II induced cardiomyocytes growth suggesting new role in cardiac hypertrophy.

• Therefore, specific identification of Wnt signaling candidate in cardiac hypertrophy may be useful for future therapeutic intervention.

Acknowledgments

The authors acknowledge RegeneRx Biopharmaceutical, Inc., for providing Tβ4 to use in this study.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosure

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was partly supported by start-up funds from the Texas A&M University, Health Science Center; American Heart Association: Grant-in-Aid (17GRNT33670897) to S. Gupta (SG). This material is the result of work supported with resources and the use of facilities at the Central Texas Veterans Affairs Health Care System, Temple, Texas. This paper has been published as part of a supplement issue covering the proceedings of the Fifth International Symposium on Thymosins in Health and Disease which is funded by SciClone Pharmaceuticals.