microRNA and thyroid hormone signaling in cardiac and skeletal muscle

Abstract

Thyroid hormone (TH) signaling plays critical roles in the differentiation, growth, metabolism, and physiological function of all organs or tissues, including heart and skeletal muscle. Due to the significant progress in our understanding of the molecular mechanisms that underlie TH action, it’s widely accepted that TH signaling is regulated at multiple levels. A growing number of discoveries suggest that microRNAs (miRNAs) act as fine-tune regulators of gene expression and adds sophisticated regulatory tiers to signaling pathways. Recently, some pioneering studies in cardiac and skeletal muscle demonstrating the interplay between miRNAs and TH signaling suggest that miRNAs might mediate and/or modulate TH signaling. This review presents recent advances involving the crosstalk between miRNAs and TH signaling and current evidence showing the importance of miRNA in TH signaling with particular emphasis on the study of muscle-specific miRNAs (myomiRs) in cardiac and skeletal muscle. Although the research of the reciprocal regulation of miRNAs and TH signaling is only at the beginning stage, it has already contributed to our current understanding of both TH action and miRNA biology. We also encourage further investigations to address the relative contributions of miRNAs in TH signaling under physiological and pathological conditions and how a group of miRNAs are coordinated to integrate into the complex hierarchical regulatory network of TH.

Stage-dependent cardiac regeneration inXenopusis regulated by thyroid hormone availability

“…Moreover, investigating whether TH acts directly or indirectly on heart regenerative outcome would be a promising line of inquiry. Arguing for a direct action, cardiomyocytes were shown to be TH-responsive in different species, in which a switch between fetal and adult transcriptomic programs is well documented in normal development and pathological conditions (55,56). Given our observations relative to the alteration of ECM dynamics, others cell populations, such as cardiofibroblasts, which are also sensitive to TH action (57), may be relevant to investigate.…”

Physiologic Significance of Epigenetic Regulation of Thyroid Hormone Target Gene Expression

“…MicroRNAs miRs are involved in another mechanism of epigenetic regulation of the TH targeted genes. TH is shown to regulate the levels of miR-206/miR-133b in human skeletal muscles, miR208a in the heart, and miR21 and miR181d in the liver [27]. In a mouse model of myocardial infarction, Dio3 is upregulated in cardiomyocytes to create a local hypothyroid condition to increase the regenerative capacity by switching to the fetal gene program.…”

Protein Tyrosine Phosphatase 1B Regulates MicroRNA-208b-Argonaute 2 Association and Thyroid Hormone Responsiveness in Cardiac Hypertrophy

“…Since exacerbated hypertrophy is observed in absence of β-MHC expression in PTP1B cKO mice, we reasoned that understanding how PTP1B inactivation prevents the expression of β-MHC would shed some light on the molecular pathways underlying the PTP1B cKO hypertrophic phenotype. The MHC switch is regulated by miRNAs and thyroid hormones in development and hypertrophy (38)(39)(40). Hence, we first tested whether miRNA populations were affected by PTP1B inactivation and TAC.…”

“…log 2 values relative to sham-operated hearts) (39). MiR-208a and miR-208b, respectively encoded by the myosin genes Myh6 (α-MHC) and Myh7 (β-MHC), mediate actions of thyroid hormone in the heart (40).…”

“…High target-prediction using web-databases (48,49) combined with validated studies (50,51) indicated that miR-208 isoforms target sites within the 3'UTR of THRAP1/MED13 transcripts, a component of the Mediator complex known to repress β-MHC transcription in a thyroid hormone-dependent manner (39,40). This prompted us to assess THRAP1 expression in PTP1B cKO mice subjected to TAC.…”