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

Publication ,  Journal Article
Yu, G; Tzouvelekis, A; Wang, R; Herazo-Maya, JD; Ibarra, GH; Srivastava, A; de Castro, JPW; DeIuliis, G; Ahangari, F; Woolard, T; Aurelien, N ...
Published in: Nature medicine
January 2018

Thyroid hormone (TH) is critical for the maintenance of cellular homeostasis during stress responses, but its role in lung fibrosis is unknown. Here we found that the activity and expression of iodothyronine deiodinase 2 (DIO2), an enzyme that activates TH, were higher in lungs from patients with idiopathic pulmonary fibrosis than in control individuals and were correlated with disease severity. We also found that Dio2-knockout mice exhibited enhanced bleomycin-induced lung fibrosis. Aerosolized TH delivery increased survival and resolved fibrosis in two models of pulmonary fibrosis in mice (intratracheal bleomycin and inducible TGF-β1). Sobetirome, a TH mimetic, also blunted bleomycin-induced lung fibrosis. After bleomycin-induced injury, TH promoted mitochondrial biogenesis, improved mitochondrial bioenergetics and attenuated mitochondria-regulated apoptosis in alveolar epithelial cells both in vivo and in vitro. TH did not blunt fibrosis in Ppargc1a- or Pink1-knockout mice, suggesting dependence on these pathways. We conclude that the antifibrotic properties of TH are associated with protection of alveolar epithelial cells and restoration of mitochondrial function and that TH may thus represent a potential therapy for pulmonary fibrosis.

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Published In

Nature medicine

DOI

EISSN

1546-170X

ISSN

1078-8956

Publication Date

January 2018

Volume

24

Issue

1

Start / End Page

39 / 49

Related Subject Headings

  • Thyroid Hormones
  • Pulmonary Fibrosis
  • Protein Kinases
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Molecular Mimicry
  • Mitochondria
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Iodothyronine Deiodinase Type II
 

Citation

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Chicago
ICMJE
MLA
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Yu, G., Tzouvelekis, A., Wang, R., Herazo-Maya, J. D., Ibarra, G. H., Srivastava, A., … Kaminski, N. (2018). Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function. Nature Medicine, 24(1), 39–49. https://doi.org/10.1038/nm.4447
Yu, Guoying, Argyris Tzouvelekis, Rong Wang, Jose D. Herazo-Maya, Gabriel H. Ibarra, Anup Srivastava, Joao Pedro Werneck de Castro, et al. “Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function.Nature Medicine 24, no. 1 (January 2018): 39–49. https://doi.org/10.1038/nm.4447.
Yu G, Tzouvelekis A, Wang R, Herazo-Maya JD, Ibarra GH, Srivastava A, et al. Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function. Nature medicine. 2018 Jan;24(1):39–49.
Yu, Guoying, et al. “Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function.Nature Medicine, vol. 24, no. 1, Jan. 2018, pp. 39–49. Epmc, doi:10.1038/nm.4447.
Yu G, Tzouvelekis A, Wang R, Herazo-Maya JD, Ibarra GH, Srivastava A, de Castro JPW, DeIuliis G, Ahangari F, Woolard T, Aurelien N, Arrojo E Drigo R, Gan Y, Graham M, Liu X, Homer RJ, Scanlan TS, Mannam P, Lee PJ, Herzog EL, Bianco AC, Kaminski N. Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function. Nature medicine. 2018 Jan;24(1):39–49.

Published In

Nature medicine

DOI

EISSN

1546-170X

ISSN

1078-8956

Publication Date

January 2018

Volume

24

Issue

1

Start / End Page

39 / 49

Related Subject Headings

  • Thyroid Hormones
  • Pulmonary Fibrosis
  • Protein Kinases
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Molecular Mimicry
  • Mitochondria
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Iodothyronine Deiodinase Type II