title: TGF-β and SMADs mRNA Expression in Pulmonary Sarcoidosis.
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.
authors.affiliation: Department of Pneumology and Allergy, First Chair of Internal Diseases, Medical University of Lodz, 251 Pomorska St., 92-213, Lodz, Poland.
authors.forename: W J
authors.initials: WJ
authors.lastname: Piotrowski
authors.forename: J
authors.initials: J
authors.lastname: Kiszałkiewicz
authors.forename: D
authors.initials: D
authors.lastname: Pastuszak-Lewandoska
authors.forename: A
authors.initials: A
authors.lastname: Antczak
authors.forename: P
authors.initials: P
authors.lastname: Górski
authors.forename: M
authors.initials: M
authors.lastname: Migdalska-Sęk
authors.forename: W
authors.initials: W
authors.lastname: Górski
authors.forename: K
authors.initials: K
authors.lastname: Czarnecka
authors.forename: E
authors.initials: E
authors.lastname: Nawrot
authors.forename: D
authors.initials: D
authors.lastname: Domańska
authors.forename: E
authors.initials: E
authors.lastname: Brzeziańska-Lasota
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D017565:Sarcoidosis, Pulmonary / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D051785:Smad Proteins / Q000235:genetics* / Q000378:metabolism; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; C497806:SMAD7 protein, human; D051785:Smad Proteins; D051899:Smad2 Protein; D051900:Smad3 Protein; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta