Thyroid hormone receptor α1 as a novel therapeutic target for tissue repair

Abstract

Analogies between the damaged tissue and developing organ indicate that a regulatory network that drives embryonic organ development may control aspects of tissue repair. In this regard, there is a growing body of experimental and clinical evidence showing that TH may be critical for recovery after injury. Especially TRα1 has been reported to play an essential role in cell proliferation and differentiation and thus in the process of repair/regeneration in the heart and other tissues. Patients after myocardial infarction, stroke or therapeutic interventions [such as PCI for coronary artery disease (CAD)] with lower TH levels appear to have increased morbidity and mortality. Accordingly, TH treatment in clinical settings of ischemia/reperfusion such as by-pass surgery seems to be cardioprotective against ischemic injury. Furthermore, TH therapy of donors is shown to result in organ preservation and increased numbers of donors and improved post-transplantation graft survival. TH and thyroid analogs may prove novel therapeutic agents for tissue repair.

Keywords: Thyroid hormone (TH); brain; heart failure (HF); myocardial ischemia; regeneration; repair; skeletal muscle; thyroid hormone receptor α1 (TRα1).

Figure 1

Changes in thyroid hormone signaling determine the response of the heart after ischemic injury. The initial response of the adult heart to injury involves enhanced expression of thyroid hormone receptor α1 (TRα1) contributing to dedifferentiation. In this context, low T3 blocks the regenerative response and leads to increasing dedifferentiation, dysfunction and heart failure. However, high T3 levels combined with increased expression of TRα1 (neonatal heart) lead to increased cardiac mass (proliferation and hypertrophy), redifferentiation and regeneration. ↑, increase; ↓, decrease.