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http://hdl.handle.net/1942/30813
Title: | Azithromycin Attenuates Fibroblast Growth Factors Induced Vascular Endothelial Growth Factor Via p38<sup>MAPK</sup> Signaling in Human Airway Smooth Muscle Cells | Authors: | WIDYASTUTI, Anna Vanaudenaerde, B.M. Vos, R. Dilisen, E. Verleden, S.E. De Vleeschauwer, S.I. Vaneylen, A. Mooi, W.J. de Boer, W.I. Sharma, H.S. Verleden, G.M. |
Issue Date: | 2013 | Publisher: | HUMANA PRESS INC |
Source: | Cell Biochemistry and Biophysics, 67 (2) , p. 331 -339 | Abstract: | The airways in asthma and COPD are characterized by an increase in airway smooth muscle (ASM) mass and bronchial vascular changes associated with increased expression of pro-angiogenic growth factors, such as fibroblast growth factors (FGF-1 and FGF-2) and vascular endothelial growth factor (VEGF). We investigated the contribution of FGF-1/-2 in VEGF production in ASM cells and assessed the influence of azithromycin and dexamethasone and their underlying signaling mechanisms. Growth-synchronized human ASM cells were pre-treated with MAPK inhibitors, U0126 for ERK1/2(MAPK) and SB239063 for p38(MAPK) as well as with dexamethasone or azithromycin, 30 min before incubation with FGF-1 or FGF-2. Expression of VEGF (VEGF-A, VEGF(121), and VEGF(165)) was assessed by quantitative PCR, VEGF release by ELISA and MAPK phosphorylation by Western blotting. Both FGF-1 and FGF-2 significantly induced mRNA levels of VEGF-A, VEGF(121), and VEGF(165). The VEGF protein release was increased 1.8-fold (FGF-1) and 5.5-fold (FGF-2) as compared to controls. Rapid transient increase in ERK1/2(MAPK) and p38(MAPK) phosphorylation and subsequent release of VEGF from FGF-1 or FGF-2-treated ASM cells were inhibited by respective blockers. Furthermore, azithromycin and dexamethasone significantly reduced both the VEGF release and the activation of p38(MAPK) pathway in response to FGF-1 or FGF-2 treatment. Our Results demonstrate that FGF-1 and FGF-2 up-regulate VEGF production via ERK1/2(MAPK) and p38(MAPK) pathways. Both azithromycin and dexamethasone elicited their anti-angiogenic effects via p38(MAPK) pathway in vitro, thereby suggesting a possible therapeutic approach to tackle VEGF-mediated vascular remodeling. | Keywords: | Airway smooth muscle cell;Angiogenesis;Azithromycin;Fibroblast growth factor;Mitogen-activated protein kinases;Vascular endothelial growth factor | Document URI: | http://hdl.handle.net/1942/30813 | Link to publication/dataset: | http://www.scopus.com/inward/record.url?eid=2-s2.0-84886589916&partnerID=MN8TOARS | DOI: | 10.1007/s12013-011-9331-0 | ISI #: | WOS:000326282900013 | Rights: | Springer Science+Business Media, LLC 2011 | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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