title: Expression of HIF-1A/VEGF/ING-4 Axis in Pulmonary Sarcoidosis.
abstract: Angiogenesis/angiostasis regulated by hypoxia inducible factor-1A (HIF-1A)/vascular endothelial growth factor (VEGF)/inhibitor of growth protein 4 (ING-4) axis may be crucial for the course and outcome of sarcoidosis. Overexpression of angiogenic factors (activation of VEGF through HIF-1A) may predispose to chronic course and lung fibrosis, whereas immunoangiostasis (related to an overexpression of inhibitory ING-4) may be involved in granuloma formation in early sarcoid inflammation, or sustained or recurrent formation of granulomas. In this work we investigated gene expression of HIF-1A, VEGF and ING-4 in bronchoalveolar fluid (BALF) cells and in peripheral blood (PB) lymphocytes of sarcoidosis patients (n=94), to better understand mechanisms of the disease and to search for its biomarkers. The relative gene expression level (RQ value) was analyzed by qPCR. The results were evaluated according to the presence of lung parenchymal involvement (radiological stage I vs. II-IV), acute vs. insidious onset, lung function tests, calcium metabolism parameters, percentage of lymphocytes (BALL%) and BAL CD4+/CD8+ in BALF, age, and gender. In BALF cells, the ING-4 and VEGF RQ values were increased, while HIF-1A expression was decreased. In PB lymphocytes all studied genes were overexpressed. Higher expression of HIF-1A in PB lymphocytes of patients with abnormal spirometry, and in BALF cells of patients with lung volume restriction was found. VEGF gene expression in BALF cells was also higher in patients with abnormal spirometry. These findings were in line with previous data on the role of HIF-1A/VEGF/ING-4 axis in the pathogenesis of sarcoidosis. Up-regulated HIF-1A and VEGF genes are linked to acknowledged negative prognostics.
authors.affiliation: Department of Pneumology and Allergy, 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: P
authors.initials: P
authors.lastname: Górski
authors.forename: A
authors.initials: A
authors.lastname: Antczak
authors.forename: M
authors.initials: M
authors.lastname: Migdalska-Sęk
authors.forename: W
authors.initials: W
authors.lastname: Górski
authors.forename: K H
authors.initials: KH
authors.lastname: Czarnecka
authors.forename: D
authors.initials: D
authors.lastname: Domańska
authors.forename: E
authors.initials: E
authors.lastname: Nawrot
authors.forename: E
authors.initials: E
authors.lastname: Brzeziańska-Lasota
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000503:physiopathology; D008214:Lymphocytes / Q000378:metabolism; D017565:Sarcoidosis, Pulmonary / Q000209:etiology* / Q000503:physiopathology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; C497442:HIF1A protein, human; D018398:Homeodomain Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C483230:ING4 protein, human; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A