Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function

Area of Science:

• Pulmonary medicine
• Endocrinology
• Cellular biology

Background:

• Thyroid hormone (TH) is vital for cellular homeostasis during stress.
• The role of TH in lung fibrosis remains largely unexplored.
• Iodothyronine deiodinase 2 (DIO2) activates TH.

Purpose of the Study:

• To investigate the role of TH and DIO2 in idiopathic pulmonary fibrosis (IPF).
• To explore TH as a potential therapeutic agent for lung fibrosis.

Main Methods:

• Assessed DIO2 activity and expression in IPF patient lungs.
• Utilized Dio2-knockout mice and bleomycin-induced lung fibrosis models.
• Administered aerosolized TH and a TH mimetic (Sobetirome).
• Examined mitochondrial biogenesis, bioenergetics, and apoptosis in alveolar epithelial cells.

Main Results:

• DIO2 activity and expression were elevated in IPF lungs, correlating with disease severity.
• Dio2-knockout mice showed exacerbated bleomycin-induced lung fibrosis.
• TH treatment improved survival and resolved fibrosis in mouse models.
• TH enhanced mitochondrial function and reduced apoptosis in alveolar cells, dependent on Ppargc1a and Pink1 pathways.

Conclusions:

• TH exhibits antifibrotic properties by protecting alveolar epithelial cells and restoring mitochondrial function.
• TH may represent a promising therapeutic strategy for pulmonary fibrosis.