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TGF-β and SMADs mRNA Expression in Pulmonary Sarcoidosis

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Respiratory Carcinogenesis

Part of the book series: Advances in Experimental Medicine and Biology ((NR,volume 852))

Abstract

Lung fibrosis is a complication of sarcoidosis, in which TGF-β/Smad pathway may play an important role. We evaluated gene expression of TGF-β1, SMAD2, 3 and 7 in bronchoalveolar lavage (BAL) cells and peripheral blood (PB) lymphocytes of sarcoidosis patients (n = 94) to better understand the mechanisms of sarcoid inflammation. The relative gene expression was analyzed by qPCR method. Selected clinical/radiological features and biochemical markers were taken into account in the analysis. We found that TGF-β1 and SMAD3 expressions in PB lymphocytes were significantly higher in sarcoidosis patients. Up-regulation of SMAD7 (inhibitory Smad) and down-regulation of SMAD3 in BAL cells in all subgroups were found. The expression of TGF-β1 in PB lymphocytes was the highest in patients with lung parenchymal involvement and in the insidious onset phenotype. The expression of TGF-β1 in BAL cells was higher in patients with abnormal spirometry (p = 0.012), and TGF-β1 and SMAD3 in patients with restrictive pattern (p = 0.034 and 0.031, respectively). Several statistically significant negative correlations were found between the expression levels of SMAD2 and 3 in BAL cells and various LFT parameters. We conclude that TGF-β/Smad pathway is involved in the pathogenesis of pulmonary sarcoidosis. These biomarkers (especially TGF-β1, SMAD2 and 3) are of a negative prognostic value.

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References

  • American Thoracic Society: European Respiratory Society: World Association of Sarcoidosis and Other Granulomatous Disorders (1999) Statement on sarcoidosis. Am J Respir Crit Care Med 160:736–755

    Article  Google Scholar 

  • Ashcroft GS, Roberts AB (2000) Loss of Smad3 modulates wound healing. Cytokine Growth Factor Rev 11:125–131

    Article  CAS  PubMed  Google Scholar 

  • Ashcroft GS, Yang X, Glick A, Weinstein M, Letterio JJ, Mizel DE (1999) Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nat Cell Biol 1:260–266

    Article  CAS  PubMed  Google Scholar 

  • Chciałowski A, Chorostowska-Wynimko J, Fal A, Pawłowicz R, Domagał-Kulawik J (2011) Recommendation of the Polish Respiratory Society for bronchoalveolar lavage (BAL) sampling processing and analysis methods. Pneumonol Alergol Pol 79:75–89

    PubMed  Google Scholar 

  • Derynck R, Zhang Y, Feng XH (1998) Smads: transcriptional activators of TGF-beta response. Cell 95:737–740

    Article  CAS  PubMed  Google Scholar 

  • European Respiratory Society (1993) Standardized lung function testing. Official statement of the European Respiratory Society. Eur Respir J 16(Suppl):1–100

    Google Scholar 

  • Flanders KC, Sullivan CD, Fuji M, Sowers A, Anzano MA, Arabshahi A, Major C, Deng C, Russo A, Mitchell JB, Roberts AB (2002) Mice lacking Smad3 are protected against cutaneous injury induced by ionizing radiation. Am J Pathol 160:1057–1068

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ianuzzi MC, Rybicki BA, Teirstein AS (2007) Medical progress. Sarcoidosis. N Engl J Med 357:2153–2165

    Article  Google Scholar 

  • Ishioka S, Saito T, Hiyama K, Haruta Y, Maeda A, Hozawa S, Inamizu T, Yamakido M (1996) Increased expression of tumor necrosis factor-alpha, interleukin-6, platelet-derived growth factor-B and granulocyte-macrophage colony-stimulating factor mRNA in cells of bronchoalveolar lavage fluids from patients with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 13:139–145

    CAS  PubMed  Google Scholar 

  • Khalil N, O’Connor RN, Flanders KC, Unruh H (1996) TGF-beta 1, but not TGF-beta 2 or TGF-beta 3, is differentially present in epithelial cells of advanced pulmonary fibrosis: an immunohistochemical study. Am J Respir Cell Mol Biol 14:131–138

    Article  CAS  PubMed  Google Scholar 

  • Kim S, Lim JH, Woo CH (2013) ERK5 inhibition ameliorates pulmonary fibrosis via regulating Smad3 acetylation. Am J Pathol 183:1758–1768

    Article  CAS  PubMed  Google Scholar 

  • Massague J (1998) TGF-beta signaling transduction. Annu Rev Biochem 67:753–791

    Article  CAS  PubMed  Google Scholar 

  • Patterson KC, Hogarth K, Husain AN, Sperling AI, Niewold TB (2012) The clinical and immunologic features of pulmonary fibrosis in sarcoidosis. Transl Res 160:321–331

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Polish Respiratory Society Guidelines for Spirometry (2006) Zalecenia Polskiego Towarzystwa Chorób Płuc dotyczce wykonywania badań spirometrycznych. Pneumonologia i Alergologia Polska 74(Suppl 1) (in Polish)

    Google Scholar 

  • Salez F, Gosset P, Copin MC, Lamblin Degros C, Tonnel AB, Wallaert B (1998) Transforming growth factor-β1 in sarcoidosis. Eur Respir J 12:913–919

    Article  CAS  PubMed  Google Scholar 

  • Schwartze JT, Becker S, Sakkas E, Wujak ŁA, Niess G, Usemann J, Reichenberger F, Herold S, Vadász I, Mayer K, Seeger W, Morty RE (2014) Glucocorticoids recruit Tgfbr3 and Smad1 to shift transforming growth factor-β signaling from the Tgfbr1/Smad2/3 axis to the Acvrl1/Smad1 axis in lung fibroblasts. J Biol Chem 289:3262–3275

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Shi K, Jiang J, Ma T, Xie J, Duan L, Chen R, Song P, Yu Z, Liu C, Zhu Q, Zheng J (2014) Pathogenesis pathways of idiopathic pulmonary fibrosis in bleomycin-induced lung injury model in mice. Respir Physiol Neurobiol 190:113–117

    Google Scholar 

  • Szlubowski A, Soja J, Grzanka P, Tomaszewska R, Papla B, Kużdżał J, Ćmiel A, Sładek K (2010) TGF-b1 in bronchoalveolar lavage fluid in diffuse parenchymal lung diseases and high-resolution computed tomography score. Pol Arch Med Wewn 120:270–275

    CAS  PubMed  Google Scholar 

  • Tang YJ, Xiao J, Huang XR, Zhang Y, Yang C, Meng XM, Feng YL, Wang XJ, Hui DS, Yu CM, Lan HY (2014) Latent TGF-β1 protects against bleomycin-induced lung injury in mice. Am J Respir Cell Mol Biol (Epub ahead of print), 51(6):761–771

    Google Scholar 

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Acknowledgements

The study was funded by grant 2011/01/B/NZ5/04239 from the National Science Center.

Conflicts of Interest

The authors declare no conflicts of interest in relation to this article.

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Authors and Affiliations

  1. Department of Pneumology and Allergy, First Chair of Internal Diseases, Medical University of Lodz, 251 Pomorska St., 92-213, Lodz, Poland

    W. J. Piotrowski, P. Górski & W. Górski

  2. Department of Molecular Bases of Medicine, First Chair of Internal Diseases, Medical University of Lodz, 251 Pomorska St., 92-213, Lodz, Poland

    J. Kiszałkiewicz, D. Pastuszak-Lewandoska, M. Migdalska-Sęk, K. Czarnecka, E. Nawrot, D. Domańska & E. Brzeziańska-Lasota

  3. Department of General and Oncological Pulmonology, First Chair of Internal Diseases, Medical University of Lodz, 251 Pomorska St., 92-213, Lodz, Poland

    A. Antczak

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  1. W. J. Piotrowski
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  2. J. Kiszałkiewicz
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  3. D. Pastuszak-Lewandoska
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  4. A. Antczak
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  5. P. Górski
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  6. M. Migdalska-Sęk
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  7. W. Górski
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  8. K. Czarnecka
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  9. E. Nawrot
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  11. E. Brzeziańska-Lasota
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Corresponding author

Correspondence to E. Brzeziańska-Lasota .

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Editors and Affiliations

  1. University of Opole Institute of Psychology, Opole, Poland

    Mieczyslaw Pokorski

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© 2014 Springer International Publishing Switzerland

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Piotrowski, W.J. et al. (2014). TGF-β and SMADs mRNA Expression in Pulmonary Sarcoidosis. In: Pokorski, M. (eds) Respiratory Carcinogenesis. Advances in Experimental Medicine and Biology(), vol 852. Springer, Cham. https://doi.org/10.1007/5584_2014_106

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