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Immunoexpression of TGF-β/Smad and VEGF-A proteins in serum and BAL fluid of sarcoidosis patients.

Piotrowski WJ, Kiszałkiewicz J, Górski P, Antczak A, Górski W, Pastuszak-Lewandoska D, Migdalska-Sęk M, Domańska-Senderowska D, Nawrot E, Czarnecka KH, Kurmanowska Z, Brzeziańska-Lasota E - BMC Immunol. (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pneumonology and Allergy, 1st Chair of Internal Medicine, Medical University of Lodz, Lodz, Poland. wojciech.piotrowski@umed.lodz.pl.

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.

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Box and whisker plots presenting statistically significant differences between patients and controls for Smad 2 (P = 0.01, U Mann–Whitney test)
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Fig2: Box and whisker plots presenting statistically significant differences between patients and controls for Smad 2 (P = 0.01, U Mann–Whitney test)

Mentions: Statistically significant differences between patients and controls were observed for TGF-β1 (P = 0.03, U Mann- Whitney test), Smad 2 (P = 0.01, U Mann–Whitney test) and for VEGF-A (P = 0.0002, U Mann–Whitney test), with higher immunoexpression levels in sarcoidosis patients (see Figs. 1, 2, and 3).Fig. 1


Immunoexpression of TGF-β/Smad and VEGF-A proteins in serum and BAL fluid of sarcoidosis patients.

Piotrowski WJ, Kiszałkiewicz J, Górski P, Antczak A, Górski W, Pastuszak-Lewandoska D, Migdalska-Sęk M, Domańska-Senderowska D, Nawrot E, Czarnecka KH, Kurmanowska Z, Brzeziańska-Lasota E - BMC Immunol. (2015)

Box and whisker plots presenting statistically significant differences between patients and controls for Smad 2 (P = 0.01, U Mann–Whitney test)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4595252&req=5

Fig2: Box and whisker plots presenting statistically significant differences between patients and controls for Smad 2 (P = 0.01, U Mann–Whitney test)
Mentions: Statistically significant differences between patients and controls were observed for TGF-β1 (P = 0.03, U Mann- Whitney test), Smad 2 (P = 0.01, U Mann–Whitney test) and for VEGF-A (P = 0.0002, U Mann–Whitney test), with higher immunoexpression levels in sarcoidosis patients (see Figs. 1, 2, and 3).Fig. 1

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pneumonology and Allergy, 1st Chair of Internal Medicine, Medical University of Lodz, Lodz, Poland. wojciech.piotrowski@umed.lodz.pl.

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.

Show MeSH
Related in: MedlinePlus