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Background: We have previously discovered that DIO2, the enzyme that catalyzes the conversion of T4 to active T3 was one of the most significantly upregulated in the lungs of patients with Idiopathic Pulmonary Fibrosis (IPF) and that its over-expression was observed specifically in alveolar cells.

Objective: We aimed to determine the role of thyroid hormone signaling in pulmonary fibrosis

Methods and results: DIO2 knockout mice developed more severe fibrosis after intratracheal administration of bleomycin compared to wild type ones, as assessed by Ashcroftscore and hydroxyproline assay (p< 0.05). Similarly, administration of propylthiouracil (PTU), an inhibitor of both T4 and T3 enhanced bleomycin induced fibrosis. Intraperitoneal delivery of T4 (40mg/kg) at days 3, and 7 following bleomycin exposure attenuated t [NK1] he fibrotic process as measured by hydroxyproline, Ashcroftscore and masson tricrome …