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Systemic Sclerosis and Serum Content of Transforming Growth Factor
Systemic sclerosis is a connective tissue disease characterized by tissue fibrosis leading to interstitial lung disease. Transforming growth factor-β (TGF-β) has been of interest as a potential diagnostic marker and also as a drug target in systemic sclerosis. The aim of this study was to assess the serum content of TGF-β1 in patients with systemic sclerosis and to assess its potential role in tissue fibrosis. The study included 30 patients, 5 men and 25 women, of the mean age of 46.9 ± 12.8 years, diagnosed with systemic sclerosis. The control group consisted of 19 women of the mean age of 28.4 ± 7.8 years, diagnosed with primary Raynaud’s disease. TGF-β1 serum levels were measured, chest imaging examinations were performed, and fibrotic tissue changes were assessed using the modified Rodnan Skin Score. We found that the mean serum TGF-β1 content in patients with systemic sclerosis was 598.7 ± 242.6 pg/mL, whereas it was 568.4 ± 322.2 pg/mL in the control group (p = 0.378). We also failed to substantiate any significant relationship between TGF-β1 serum levels and the severity of pulmonary and skin fibrosis in systemic sclerosis. In conclusion, systemic sclerosis does not seem a disease that would be accompanied by a specific enhancement of serum TGF-β1. Thus, this cytokine is rather unlikely to play an essential role in the development and course of the disease, nor can it be considered diagnostic or prognostic marker.
KeywordsConnective tissue disease Cytokines Fibroblasts Pulmonary hypertension Rheumatology Scleroderma
Conflicts of Interest
The authors declare no conflicts of interest in relation to this article.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the Bioethics Committee of the Karol Marcinkowski University of Medical Sciences in Poznań, Poland.
Informed consent was obtained from all individual participants included in the study.
- Akesson A, Fiori G, Krieg T, van den Hoogen FHJ, Seibold JR (2003) Assessment of skin, joint, tendon and muscle involvement. Clin Exp Rheumatol 21:S5–S8Google Scholar
- Border WA, Noble NA (1994) Transforming growth factor beta in tissue fibrosis. N Engl J Med 331:1286–1292Google Scholar
- Border WA, Ruoslahti E (1992) Transforming growth factor-beta in disease: the dark side of tissue repair. J Clin Invest 90:1–7Google Scholar
- Clements PJ (2000) Systemic sclerosis (scleroderma) and related disorders: clinical aspects. Baillieres Best Pract Res Clin Rheumatol 14:1–16Google Scholar
- Collier D (2002) Systemic sclerosis. In: West S (ed) Rheumatology secrets, 2nd edn. Hanley & Belfus, PhiladelphiaGoogle Scholar
- Cutolo M, Smith V, Furst DE, Khanna D, Herrick AL (2017) Points to consider-Raynaud's phenomenon in systemic sclerosis. Rheumatology (Oxford) 56(Suppl 5):v45–v48Google Scholar
- Dantas AT, Gonçalves SM, de Almeida AR, Gonçalves RS, Sampaio MC, Vilar KM, Pereira MC, Rêgo MJ, Pitta ID, Marques CD, Duarte AL, Pitta MG (2016) Reassessing the role of the active TGF-β1 as a biomarker in systemic sclerosis: association of serum levels with clinical manifestations. Dis Markers 2016:6064830Google Scholar
- Denton CP, Black CM (2004) Scleroderma – clinical and pathological advances. Best Pract Res Clin Rheumatol 18:271–290Google Scholar
- Du J, Yu Y, Zhan J, Zhang H (2017) Targeted therapies against growth factor signaling in breast cancer. Adv Exp Med Biol 1026:125–146Google Scholar
- Dziadzio M, Smith RE, Abraham DJ, Black CM, Denton CP (2005) Circulating levels of active transforming growth factor beta1 are reduced in diffuse cutaneous systemic sclerosis and correlate inversely with the modified Rodnan skin score. Rheumatology (Oxford) 44:1518–1524Google Scholar
- Jakubowska K, Naumnik W, Niklińska W, Chyczewska E (2015) Clinical significance of HMGB-1 and TGF-β level in serum and BALF of advanced non-small cell lung cancer. Adv Exp Med Biol 852:49–58Google Scholar
- Klippel JH, Dieppe PA (1998) Rheumatology, 2nd edn. Mosby, LondonGoogle Scholar
- Lafyatis R (2014) Transforming growth factor β – at the centre of systemic sclerosis. Nat Rev Rheumatol 10:706–719Google Scholar
- Leask A (2006) Scar wars: is TGFbeta the phantom menace in scleroderma? Arthritis Res Ther 8:213–219Google Scholar
- Piorunek T, Kuznar-Kaminska B, Cofta S, Batura-Gabryel H, Poplawski D, Majewski D, Puszczewicz M, Wysocka E (2013) Lung impairment in scleroderma. Adv Exp Med Biol 755:149–154Google Scholar
- Piotrowski WJ, Kiszałkiewicz J, Pastuszak-Lewandoska D, Antczak A, Górski P, Migdalska-Sęk M, Górski W, Czarnecka K, Nawrot E, Domańska D, Brzeziańska-Lasota E (2015) TGF-β and Smads mRNA expression in pulmonary sarcoidosis. Adv Exp Med Biol 852:59–69Google Scholar
- Scala E, Pallotta S, Frezzolini A, Abeni D, Barbieri C, Sampogna F, De Pità O, Puddu P, Paganelli R, Russo G (2004) Cytokine and chemokine levels in systemic sclerosis: relationship with cutaneous and internal organ involvement. Clin Exp Immunol 138:540–546Google Scholar
- Snowden N, Coupes B, Herrick A, Illingworth K, Jayson MI, Brenchley PE (1994) Plasma TGF beta in systemic sclerosis: a cross-sectional study. Ann Rheum Dis 53:763–767Google Scholar
- Verrecchia F, Mauviel A, Farge D (2006) Transforming growth factor-beta signaling through the Smad proteins: role in systemic sclerosis. Autoimmun Rev 5:563–569Google Scholar
- Wakefield LM, Winokur TS, Hollands RS, Christopherson K, Levinson AD, Sporn MB (1990) Recombinant latent transforming growth factor beta 1 has a longer plasma half-life in rats than active transforming growth factor beta 1, and a different tissue distribution. J Clin Invest 86:1976–1984Google Scholar
- Wermuth PJ, Jimenez SA (2018) Abrogation of transforming growth factor-β-induced tissue fibrosis in TBRIcaCol1a2Cre transgenic mice by the second generation tyrosine kinase inhibitor SKI-606 (Bosutinib). PLoS One 13:e0196559Google Scholar