Molecular Basis of T3 non-genomic actions in myocytes and pancreatic beta cells - expression profiling of microRNAs, in vivo, in rats treated with T3

Abstract

Thyroid hormones (THs) play critical roles in differentiation, growth, and metabolism. THs can rapidly generate biological responses by non-genomic mechanisms, that are unaffected by inhibitors of transcription and translation. The signal transduction pathways underlying these effects are just beginning to be dened. Considering that T3-induced signaling pathways can influence relevant physiological process, as glucose uptake, and their deregulation might play an important role in disease states, e.g. gastric cancer; thus, it is of major importance to fully comprehend them. To our knowledge, we still lack a complete description of the T3-induced pathway(s) and downstream targets in myocytes, which are a major target of T3. Thus, we will attempt to identify the components of the signaling pathway(s) responsible for T3 non-genomic actions in myocytes. We showed that T3 increases insulin synthesis and activates specific translational factors in pancreatic beta cells. However, T3 actions on components of the protein synthesis machinery have been poorly explored. Therefore, we will determine the components of the T3-induced pathway responsible for this activation in pancreatic beta cells and extend these studies to myocytes. Moreover, THs regulate the expression of small non-coding mRNAs (miRNAs), which in turn control gene expression at the post-transcriptional level. We demonstrated that treatment of rat cardiomyocytes with T3, in vitro, induces miR-350 expression. Strikingly there is remarkable lack of data for the role of T3 on miRNAs expression, in vivo, in humans and other species. Thus we intend to identify, using miRNA expression profiling, the miRNAs that are regulated by T3 in various tissues and determine the downstream target genes of the differentially expressed miRNAs, in vivo, in rats.