title: Expression analysis of angiogenic growth factors and biological axis CXCL12/CXCR4 axis in idiopathic pulmonary fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF) is associated with aberrant repair, persistence of collagen deposition, and the development of vascular remodeling. However, the role of angiogenesis in the pathogenesis of IPF is still undetermined. The aim of this study was to evaluate the combined mRNA expression of vascular endothelial growth factor A (VEGFA), fibroblast growth factor 2 (FGF2), insulin-like growth factor 1 (IGF1) epidermal growth factor (EGF), and its receptor (EGFR) in lung tissue obtained from IPF patients. We have also investigated the expression of chemokine CXCL12/stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, to identify alterations that maybe implicated in the pathogenesis of IPF. The subjects studied consisted of two distinct groups: patients with IPF (n = 25) and subjects (control) undergoing thoracic surgery for reasons other than interstitial lung disease (n = 10). Expression analysis of the aforementioned growth factors and biological axis CXCL12/CXR4 analysis were performed using real-time RT-PCR. IGF-1, EGF, and FGF2 mRNA levels are significantly decreased in the patients compared to the controls (p = 0.028, p = 0.023 and p = 0.009, respectively). SDF1-TR1 and SDF1-TR2 transcript levels were significantly lower in patients compared to controls (p = 0.017 and p = 0.001). Significant coexpression of VEGF mRNA with IGF mRNA was observed in the group of the patients (p = 0.017). An additional coexpression of VEGF mRNA with SDF1-TR1 mRNA was demonstrated(p = 0.030). Our results show a downregulation in angiogenetic mechanisms in IPF. However, our results should be further verified by measuring other angiogenetic pathways in more samples.
authors.affiliation: Department of Thoracic Medicine, Interstitial Lung Disease Unit, Medical School, University of Crete, Heraklion, Crete, Greece.
authors.forename: Katerina M
authors.initials: KM
authors.lastname: Antoniou
authors.forename: Giannoula
authors.initials: G
authors.lastname: Soufla
authors.forename: Rena
authors.initials: R
authors.lastname: Lymbouridou
authors.forename: Foteini
authors.initials: F
authors.lastname: Economidou
authors.forename: Ismini
authors.initials: I
authors.lastname: Lasithiotaki
authors.forename: Manolis
authors.initials: M
authors.lastname: Manousakis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Drositis
authors.forename: Demetrios A
authors.initials: DA
authors.lastname: Spandidos
authors.forename: Nikolaos M
authors.initials: NM
authors.lastname: Siafakas
mesh_terms: D042501:Angiogenic Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D004815:Epidermal Growth Factor / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D042501:Angiogenic Proteins; D015415:Biomarkers; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D012333:RNA, Messenger; D019718:Receptors, CXCR4; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; C512478:EGFR protein, human; D066246:ErbB Receptors