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Reducing protein oxidation reverses lung fibrosis

Nature Medicine volume 24, pages 1128–1135 (2018)Cite this article

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Abstract

Idiopathic pulmonary fibrosis is characterized by excessive deposition of collagen in the lung, leading to chronically impaired gas exchange and death1,2,3. Oxidative stress is believed to be critical in this disease pathogenesis4,5,6, although the exact mechanisms remain enigmatic. Protein S-glutathionylation (PSSG) is a post-translational modification of proteins that can be reversed by glutaredoxin-1 (GLRX)7. It remains unknown whether GLRX and PSSG play a role in lung fibrosis. Here, we explored the impact of GLRX and PSSG status on the pathogenesis of pulmonary fibrosis, using lung tissues from subjects with idiopathic pulmonary fibrosis, transgenic mouse models and direct administration of recombinant Glrx to airways of mice with existing fibrosis. We demonstrate that GLRX enzymatic activity was strongly decreased in fibrotic lungs, in accordance with increases in PSSG. Mice lacking Glrx were far more susceptible to bleomycin- or adenovirus encoding active transforming growth factor beta-1 (AdTGFB1)-induced pulmonary fibrosis, whereas transgenic overexpression of Glrx in the lung epithelium attenuated fibrosis. We furthermore show that endogenous GLRX was inactivated through an oxidative mechanism and that direct administration of the Glrx protein into airways augmented Glrx activity and reversed increases in collagen in mice with TGFB1- or bleomycin-induced fibrosis, even when administered to fibrotic, aged animals. Collectively, these findings suggest the therapeutic potential of exogenous GLRX in treating lung fibrosis.

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Fig. 1: Lower glutaredoxin-1 (GLRX) enzymatic activity and higher protein PSSG occur in lung tissues from subjects with IPF and correlate with disease severity.
Fig. 2: Bleomycin-induced lung fibrosis and PSSG are elevated in Glrx−/− mice and lowered following transgenic overexpression of Glrx in lung epithelial cells.
Fig. 3: Direct administration of recombinant Glrx to the lung protects against the progression of and reverses existing pulmonary fibrosis.
Fig. 4: Ageing-associated enhanced susceptibility to pulmonary fibrosis induced by bleomycin is associated with low Glrx activity and can be rescued following oropharyngeal administration of Glrx.

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References

  1. du Bois, R. M. Strategies for treating idiopathic pulmonary fibrosis. Nat. Rev. Drug Discov. 9, 129–140 (2010).

    PubMed  Google Scholar 

  2. Barkauskas, C. E. & Noble, P. W. Cellular mechanisms of tissue fibrosis. 7. New insights into the cellular mechanisms of pulmonary fibrosis. Am. J. Physiol. Cell Physiol. 306, C987–996 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Raghu, G. et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am. J. Respir. Crit. Care Med. 183, 788–824 (2011).

    PubMed  PubMed Central  Google Scholar 

  4. Kinnula, V. L. & Myllarniemi, M. Oxidant–antioxidant imbalance as a potential contributor to the progression of human pulmonary fibrosis. Antioxid. Redox Signal. 10, 727–738 (2008).

    CAS  PubMed  Google Scholar 

  5. Janssen-Heininger, Y. M. et al. Regulation of apoptosis through cysteine oxidation: implications for fibrotic lung disease. Ann. NY Acad. Sci. 1203, 23–28 (2010).

    CAS  PubMed  Google Scholar 

  6. Kurundkar, A. & Thannickal, V. J. Redox mechanisms in age-related lung fibrosis. Redox Biol. 9, 67–76 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Mieyal, J. J., Gallogly, M. M., Qanungo, S., Sabens, E. A. & Shelton, M. D. Molecular mechanisms and clinical implications of reversible protein S-glutathionylation. Antioxid. Redox Signal. 10, 1941–1988 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Cantin, A. M., Hubbard, R. C. & Crystal, R. G. Glutathione deficiency in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis. Am. Rev. Respir. Dis. 139, 370–372 (1989).

    CAS  PubMed  Google Scholar 

  9. Beeh, K. M. et al. Glutathione deficiency of the lower respiratory tract in subjects with idiopathic pulmonary fibrosis. Eur. Respir. J. 19, 1119–1123 (2002).

    CAS  PubMed  Google Scholar 

  10. Rahman, I. et al. Systemic and pulmonary oxidative stress in idiopathic pulmonary fibrosis. Free Radic. Biol. Med. 27, 60–68 (1999).

    CAS  PubMed  Google Scholar 

  11. Meyer, A., Buhl, R. & Magnussen, H. The effect of oral N-acetylcysteine on lung glutathione levels in idiopathic pulmonary fibrosis. Eur. Respir. J. 7, 431–436 (1994).

    CAS  PubMed  Google Scholar 

  12. Shahzeidi, S., Sarnstrand, B., Jeffery, P. K., McAnulty, R. J. & Laurent, G. J. Oral N-acetylcysteine reduces bleomycin-induced collagen deposition in the lungs of mice. Eur. Respir. J. 4, 845–852 (1991).

    CAS  PubMed  Google Scholar 

  13. Hagiwara, S. I., Ishii, Y. & Kitamura, S. Aerosolized administration of N-acetylcysteine attenuates lung fibrosis induced by bleomycin in mice. Am. J. Respir. Crit. Care Med. 162, 225–231 (2000).

    CAS  PubMed  Google Scholar 

  14. Demedts, M. et al. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N. Engl. J. Med. 353, 2229–2242 (2005).

    CAS  PubMed  Google Scholar 

  15. Martinez, F. J., de Andrade, J. A., Anstrom, K. J., King, T. E. Jr. & Raghu, G. Randomized trial of acetylcysteine in idiopathic pulmonary fibrosis. N. Engl. J. Med. 370, 2093–2101 (2014).

    PubMed  PubMed Central  Google Scholar 

  16. Janssen-Heininger, Y. M. et al. Redox-based regulation of signal transduction: principles, pitfalls, and promises. Free Radic. Biol. Med. 45, 1–17 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Aesif, S. W. et al. In situ analysis of protein S-glutathionylation in lung tissue using glutaredoxin-1-catalyzed cysteine derivatization. Am. J. Pathol. 175, 36–45 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Kuwano, K. et al. Essential roles of the Fas–Fas ligand pathway in the development of pulmonary fibrosis. J. Clin. Invest. 104, 13–19 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Anathy, V. et al. Redox amplification of apoptosis by caspase-dependent cleavage of glutaredoxin 1 and S-glutathionylation of Fas. J. Cell Biol. 184, 241–252 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Hagimoto, N. et al. Induction of apoptosis and pulmonary fibrosis in mice in response to ligation of Fas antigen. Am. J. Respir. Cell Mol. Biol. 17, 272–278 (1997).

    CAS  PubMed  Google Scholar 

  21. Sisson, T. H. et al. Targeted injury of type II alveolar epithelial cells induces pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 181, 254–263 (2010).

    CAS  PubMed  Google Scholar 

  22. Liang, J. et al. Hyaluronan and TLR4 promote surfactant-protein-C-positive alveolar progenitor cell renewal and prevent severe pulmonary fibrosis in mice. Nat. Med. 22, 1285–1293 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Korfei, M. et al. Epithelial endoplasmic reticulum stress and apoptosis in sporadic idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 178, 838–846 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Degryse, A. L. et al. TGFβ signaling in lung epithelium regulates bleomycin-induced alveolar injury and fibroblast recruitment. Am. J. Physiol. Lung Cell Mol. Physiol. 300, L887–897 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Anathy, V. et al. Glutaredoxin-1 attenuates S-glutathionylation of the death receptor Fas and decreases resolution of Pseudomonas aeruginosa pneumonia. Am. J. Respir. Crit. Care Med. 189, 463–474 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Sime, P. J., Xing, Z., Graham, F. L., Csaky, K. G. & Gauldie, J. Adenovector-mediated gene transfer of active transforming growth factor-β1 induces prolonged severe fibrosis in rat lung. J. Clin. Invest. 100, 768–776 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Hashemy, S. I., Johansson, C., Berndt, C., Lillig, C. H. & Holmgren, A. Oxidation and S-nitrosylation of cysteines in human cytosolic and mitochondrial glutaredoxins: effects on structure and activity. J. Biol. Chem. 282, 14428–14436 (2007).

    CAS  PubMed  Google Scholar 

  28. Selman, M. & Pardo, A. Revealing the pathogenic and aging-related mechanisms of the enigmatic idiopathic pulmonary fibrosis. An integral model. Am. J. Respir. Crit. Care Med. 189, 1161–1172 (2014).

    CAS  PubMed  Google Scholar 

  29. Mora, A. L., Rojas, M., Pardo, A. & Selman, M. Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease. Nat. Rev. Drug Discov. 16, 810 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Hecker, L. et al. Reversal of persistent fibrosis in aging by targeting Nox4–Nrf2 redox imbalance. Sci. Transl. Med. 6, 231ra247 (2014).

    Google Scholar 

  31. Kropski, J. A. & Blackwell, T. S. Endoplasmic reticulum stress in the pathogenesis of fibrotic disease. J. Clin. Invest. 128, 64–73 (2018).

    PubMed  PubMed Central  Google Scholar 

  32. Thannickal, V. J. & Horowitz, J. C. Evolving concepts of apoptosis in idiopathic pulmonary fibrosis. Proc. Am. Thorac. Soc. 3, 350–356 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. King, T. E. Jr et al. A phase 3 trial of pirfenidone in subjects with idiopathic pulmonary fibrosis. N. Engl. J. Med. 370, 2083–2092 (2014).

    PubMed  Google Scholar 

  34. Richeldi, L. et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N. Engl. J. Med. 370, 2071–2082 (2014).

    PubMed  Google Scholar 

  35. Lillig, C. H., Berndt, C. & Holmgren, A. Glutaredoxin systems. Biochim. Biophys. Acta 1780, 1304–1317 (2008).

    CAS  PubMed  Google Scholar 

  36. Wu, R. F., Ma, Z., Liu, Z. & Terada, L. S. Nox4-derived H2O2 mediates endoplasmic reticulum signaling through local Ras activation. Mol. Cell. Biol. 30, 3553–3568 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Carnesecchi, S. et al. A key role for NOX4 in epithelial cell death during development of lung fibrosis. Antioxid. Redox Signal. 15, 607–619 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Anathy, V. et al. Oxidative processing of latent Fas in the endoplasmic reticulum controls the strength of apoptosis. Mol. Cell. Biol. 32, 3464–3478 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Bueno, M. et al. PINK1 deficiency impairs mitochondrial homeostasis and promotes lung fibrosis. J. Clin. Invest. 125, 521–538 (2015).

    PubMed  Google Scholar 

  40. Mora, A. L., Bueno, M. & Rojas, M. Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis. J. Clin. Invest. 127, 405–414 (2017).

    PubMed  PubMed Central  Google Scholar 

  41. Perl, A. K., Zhang, L. & Whitsett, J. A. Conditional expression of genes in the respiratory epithelium in transgenic mice: cautionary notes and toward building a better mouse trap. Am. J. Respir. Cell Mol. Biol. 40, 1–3 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Perl, A. K. et al. Conditional recombination reveals distinct subsets of epithelial cells in trachea, bronchi, and alveoli. Am. J. Respir. Cell Mol. Biol. 33, 455–462 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Salmena, L. et al. Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. Genes Dev. 17, 883–895 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Watanabe-Fukunaga, R., Brannan, C. I., Copeland, N. G., Jenkins, N. A. & Nagata, S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356, 314–317 (1992).

    CAS  PubMed  Google Scholar 

  45. Ho, Y. S. et al. Targeted disruption of the glutaredoxin 1 gene does not sensitize adult mice to tissue injury induced by ischemia/reperfusion and hyperoxia. Free Radic. Biol. Med. 43, 1299–1312 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Bauer, Y. et al. A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis. Am. J. Respir. Cell Mol. Biol. 52, 217–231 (2015).

    PubMed  PubMed Central  Google Scholar 

  47. R Core Team. R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, Vienna, 2011).

  48. Woessner, J. F. Jr. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch. Biochem. Biophys. 93, 440–447 (1961).

    CAS  PubMed  Google Scholar 

  49. Fonseca, C., Taatjes, D. J., Callas, P., Ittleman, F. & Bovill, E. G. The effects of aging on the intimal region of the human saphenous vein: insights from multimodal microscopy and quantitative image analysis. Histochem. Cell Biol. 138, 435–445 (2012).

    CAS  PubMed  Google Scholar 

  50. Reynaert, N. L., Wouters, E. F. & Janssen-Heininger, Y. M. Modulation of glutaredoxin-1 expression in a mouse model of allergic airway disease. Am. J. Respir. Cell Mol. Biol. 36, 147–151 (2007).

    CAS  PubMed  Google Scholar 

  51. Coppo, L., Montano, S. J., Padilla, A. C. & Holmgren, A. Determination of glutaredoxin enzyme activity and protein S-glutathionylation using fluorescent eosin-glutathione. Anal. Biochem. 499, 24–33 (2016).

    CAS  PubMed  Google Scholar 

  52. Micsonai, A. et al. Accurate secondary structure prediction and fold recognition for circular dichroism spectroscopy. Proc. Natl Acad. Sci. USA 112, E3095–3103 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Rahman, I., Kode, A. & Biswas, S. K. Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat. Protoc. 1, 3159–3165 (2006).

    CAS  PubMed  Google Scholar 

  54. Jones, P. W., Quirk, F. H., Baveystock, C. M. & Littlejohns, P. A self-complete measure of health status for chronic airflow limitation. The St. George’s Respiratory Questionnaire. Am. Rev. Respir. Dis. 145, 1321–1327 (1992).

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was funded by NIH R35HL135828, R01HL079331, R01HL060014 and R03HL095404 (Y.M.W.J.-H.), an ATS unrestricted grant and NIH R01HL122383 (V.A.), Parker B. Francis fellowships (V.A. and J.L.J.v.d.V.), NIH R01HL05646 (A.v.d.V.), T32HL076122 (D.H.M. and J.T.J.), NCRR 1S10RR019246 (D.J.T.), American Heart Association 16GRNT27660006, NIH R01DK103750 and 1UL1TR001430 (M.M.B.), NIH R01HL133013 and R03 AG051857 (R.M.), P30GM103532 (C.G.I.), FAMRI Young Clinical Scientist Award 113393 and 1K01HL125474-01 (J.L.G.) and U01HL108642 and RC2 HL101715 (N.K.). Analysis of biological specimens and data provided by the Lung Tissue Research Consortium (LTRC) was supported by R03HL095404 (Y.M.W.J.-H.). We would like to thank J. Whitsett (University of Cincinnati) for generously providing the CCSP-rtTA, TetOP-Cre mice, J. Gauldie for providing AdTGFB1, N. Bishop for help with imaging of GLRX and collagen, J. M. Siddesha for technical support and P. Vacek for statistical support.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, VT, USA

    Vikas Anathy, Karolyn G. Lahue, Shi B. Chia, Dylan T. Casey, Reem Aboushousha, Jos L. J. van der Velden, Evan Elko, Sidra M. Hoffman, David H. McMillan, Jane T. Jones, James D. Nolin, Sarah Abdalla, Robert Schneider, David J. Seward, Kelly J. Butnor, Douglas. J. Taatjes, Albert van der Vliet & Yvonne M. W. Janssen-Heininger

  2. Department of Medicine, University of Vermont, Burlington, VT, USA

    David G. Chapman, Ralph C. Budd & Charles G. Irvin

  3. Honors College, University of Vermont, Burlington, VT, USA

    Elle C. Roberson

  4. Department of Chemistry, University of Vermont, Burlington, VT, USA

    Matthew D. Liptak & Morgan E. Cousins

  5. Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, USA

    Ye-Shih Ho

  6. Department of Medical Biophysics and Immunology, University of Toronto, and the Ontario Cancer Institute/University Health Network, Toronto, Ontario, Canada

    Razq Hakem

  7. Department of Medicine, Pulmonary, Critical Care and Sleep Section, National Jewish Health and the University of Colorado, Denver, CO, USA

    Kevin K. Brown

  8. Department of Medicine, Boston University, Boston, MA, USA

    Reiko Matsui & Markus M. Bachschmid

  9. Department of Medicine, Yale School of Medicine, New Haven, CT, USA

    Jose L. Gomez & Naftali Kaminski

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  1. Vikas Anathy
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Contributions

V.A., K.G.L., S.M.H., D.H.M., J.T.J., E.E., J.D.N., D.T.C., J.L.J.v.d.V. and R.S. performed the animal experiments. S.A., S.B.C. and K.G.L. prepared and tested recombinant GLRX; V.A., S.M.H., E.C.R., R.A. and K.G.L. performed S-glutathionylation and glutaredoxin assays; K.G.L. and D.T.C. performed fibrosis analyses; K.J.B. reviewed histopathology; D.J.T. provided critical suggestions regarding imaging and image analysis. Y.-S.H. generated Glrx−/− mice and helped with data interpretation; R.A. and S.B.C. performed collagenolytic activity assays; M.D.L. and M.E.C. performed and analyzed CD studies; R.H. generated Casp8loxP/loxP mice and helped with data interpretation. R.M. and M.M.B. conducted the ageing study and participated in data analyses. A.v.d.V. and R.C.B. supported the studies with key experimental suggestions and helped interpret data. D.J.S., D.G.C., C.G.I., K.J.B., J.L.G., N.K. and K.K.B. evaluated and analyzed clinical data. Y.M.W.J.-H. and V.A. designed the research, interpreted the data and wrote the manuscript.

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Correspondence to Yvonne M. W. Janssen-Heininger.

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Competing interests

Y.M.W.J.-H. and V.A. hold patents entitled: ‘Treatments involving glutaredoxins and similar agents’, ‘Treatments of oxidative stress conditions’ (US patent no. 8,679,811 and 9,907,828; Y.M.W.J.-H. and V.A.) and ‘Detection of glutathionylated proteins’ (US patent no. 8,877,447; Y.M.W.J.-H.).

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Anathy, V., Lahue, K.G., Chapman, D.G. et al. Reducing protein oxidation reverses lung fibrosis. Nat Med 24, 1128–1135 (2018). https://doi.org/10.1038/s41591-018-0090-y

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