title: Immunoexpression of TGF-β/Smad and VEGF-A proteins in serum and BAL fluid of sarcoidosis patients.
abstract: BACKGROUND
  The chronic course of pulmonary sarcoidosis can lead to lung dysfunction due to fibrosis, in which the signalling pathways TGF-β/Smad and VEGF-A may play a key role.
  
  
  METHODS
  We evaluated immunoexpression of TGF-β1, Smad2, 3, and 7, and VEGF-A in serum and bronchoalveolar lavage (BAL) fluid of patients (n = 57) classified according to the presence of lung parenchymal involvement (radiological stage I vs. II-III), acute vs. insidious onset, lung function test (LFT) results, calcium metabolism parameters, percentage of BAL lymphocytes (BAL-L%), BAL CD4(+)/CD8(+) ratio, age, and gender. Immunoexpression analysis of proteins was performed by ELISA.
  
  
  RESULTS
  The immunoexpression of all studied proteins were higher in serum than in BAL fluid of patients (p >0.05). The serum levels of TGF-β1 (p = 0.03), Smad2 (p = 0.01), and VEGF-A (p = 0.0002) were significantly higher in sarcoidosis patients compared to healthy controls. There were no differences within the sarcoidosis group between patients with vs. without parenchymal involvement, acute vs. insidious onset, or patients with normal vs. abnormal spirometry results. In patients with abnormal spirometry results a negative correlation was found between forced vital capacity (FVC) % predicted value and TGF-β1 immunoexpression in BAL fluid, and positive correlations were observed between the intensity of lung parenchymal changes estimated by high-resolution computed tomography (HRCT scores) and Smad 2 level in serum.
  
  
  CONCLUSIONS
  TGF-β/Smad signalling pathway and VEGF-A participate in the pathogenesis of sarcoidosis. BAL TGF-β1, and Smad 2 in serum seem to be promising biomarkers with negative prognostic value, but further studies are required to confirmed our observations.
authors.affiliation: Department of Pneumonology and Allergy, 1st Chair of Internal Medicine, Medical University of Lodz, Lodz, Poland. wojciech.piotrowski@umed.lodz.pl.
authors.forename: Wojciech J
authors.initials: WJ
authors.lastname: Piotrowski
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Medicine, Medical University of Lodz, 251 Pomorska St., 92-213, Lodz, Poland. justyna.kiszalkiewicz@gmail.com.
authors.forename: Justyna
authors.initials: J
authors.lastname: Kiszałkiewicz
authors.affiliation: Department of Pneumonology and Allergy, 1st Chair of Internal Medicine, Medical University of Lodz, Lodz, Poland. pawel.gorski@umed.lodz.pl.
authors.forename: Paweł
authors.initials: P
authors.lastname: Górski
authors.affiliation: Department of General and Oncological Pulmonology, 1st Chair of Internal Medicine, Medical University of Lodz, Lodz, Poland. adam.antczak@umed.lodz.pl.
authors.forename: Adam
authors.initials: A
authors.lastname: Antczak
authors.affiliation: Department of Pneumonology and Allergy, 1st Chair of Internal Medicine, Medical University of Lodz, Lodz, Poland. mcwitek@tlen.pl.
authors.forename: Witold
authors.initials: W
authors.lastname: Górski
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Medicine, Medical University of Lodz, 251 Pomorska St., 92-213, Lodz, Poland. dorota.pastuszak-lewandoska@umed.lodz.pl.
authors.forename: Dorota
authors.initials: D
authors.lastname: Pastuszak-Lewandoska
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Medicine, Medical University of Lodz, 251 Pomorska St., 92-213, Lodz, Poland. monika.migdalska-sek@umed.lodz.pl.
authors.forename: Monika
authors.initials: M
authors.lastname: Migdalska-Sęk
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Medicine, Medical University of Lodz, 251 Pomorska St., 92-213, Lodz, Poland. daria.domanska@umed.lodz.pl.
authors.forename: Daria
authors.initials: D
authors.lastname: Domańska-Senderowska
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Medicine, Medical University of Lodz, 251 Pomorska St., 92-213, Lodz, Poland. ewa.nawrot@umed.lodz.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Nawrot
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Medicine, Medical University of Lodz, 251 Pomorska St., 92-213, Lodz, Poland. karolina.czarnecka@umed.lodz.pl.
authors.forename: Karolina H
authors.initials: KH
authors.lastname: Czarnecka
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Medicine, Medical University of Lodz, 251 Pomorska St., 92-213, Lodz, Poland. zofia_kurmanowska@tlen.pl.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Kurmanowska
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Medicine, Medical University of Lodz, 251 Pomorska St., 92-213, Lodz, Poland. ewa.brzezianska@umed.lodz.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Brzeziańska-Lasota
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D010641:Phenotype; D012129:Respiratory Function Tests; D017565:Sarcoidosis, Pulmonary / Q000097:blood* / Q000000981:diagnostic imaging / Q000276:immunology* / Q000503:physiopathology; D051785:Smad Proteins / Q000097:blood*; D014057:Tomography, X-Ray Computed; D016212:Transforming Growth Factor beta / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D015415:Biomarkers; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A