Thyroid hormone regulates muscle fiber type conversion via miR-133a1

Area of Science:

• Molecular Biology
• Endocrinology
• Muscle Physiology

Background:

• Thyroid hormone (TH) is crucial for muscle fiber composition.
• The precise molecular mechanisms underlying TH's effects on muscle are not fully understood.

Purpose of the Study:

• To elucidate the molecular pathway through which TH regulates muscle fiber type.
• To identify novel epigenetic regulators involved in TH-mediated muscle adaptation.

Main Methods:

• Investigated miR-133a1 as a direct target of TH in muscle tissue.
• Utilized in vivo inhibition of miR-133a and TEAD1 overexpression models.
• Analyzed the regulation of myosin heavy chain I (MyHC-I) transcription.

Main Results:

• miR-133a1 was identified as a direct target of TH in muscle.
• miR-133a1 targets TEAD1, a regulator of slow muscle gene expression, promoting fast-twitch fiber characteristics.
• Inhibition of miR-133a or TEAD1 overexpression reversed TH-induced muscle fiber type switching.

Conclusions:

• TH inhibits the slow muscle phenotype via an epigenetic mechanism involving miR-133a1-mediated repression of TEAD1.
• This pathway highlights a novel role for microRNAs in mediating TH's diverse biological actions on skeletal muscle.