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Home Search Quick Search Advanced Fulltext Browse Collections Persons My eDoc Session History Login Name: Password: Documentation Help Support Wiki Direct access to document ID:	Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook_2015     Display Documents ID: 711849.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook_2015 Hypoxia- or PDGF-BB-dependent paxillin tyrosine phosphorylation in pulmonary hypertension is reversed by HIF-1alpha depletion or imatinib treatment Authors: Veith, C.; Zakrzewicz, D.; Dahal, B. K.; Balint, Z.; Murmann, K.; Wygrecka, M.; Seeger, W.; Schermuly, R. T.; Weissmann, N.; Kwapiszewska, G. Date of Publication (YYYY-MM-DD): 2014-12 Title of Journal: Thromb Haemost Volume: 112 Issue / Number: 6 Start Page: 1288 End Page: 1303 Audience: Not Specified Abstract / Description: Chronic exposure to hypoxia induces a pronounced remodelling of the pulmonary vasculature leading to pulmonary hypertension (PH). The remodelling process also entails increased proliferation and decreased apoptosis of pulmonary arterial smooth muscle cells (PASMC), processes regulated by the cytoskeletal protein paxillin. In this study, we aimed to examine the molecular mechanisms leading to deregulation of paxillin in PH. We detected a time-dependent increase in paxillin tyrosine 31 (Y31) and 118 (Y118) phosphorylation following hypoxic exposure (1 % O2) or platelet-derived growth factor (PDGF)-BB stimulation of primary human PASMC. In addition, both, hypoxia- and PDGF-BB increased the nuclear localisation of phospho-paxillin Y31 as indicated by immunofluorescence staining in human PASMC. Elevated paxillin tyrosine phosphorylation in human PASMC was attenuated by hypoxia-inducible factor (HIF)-1alpha depletion or by treatment with the PDGF-BB receptor antagonist, imatinib. Moreover, we observed elevated paxillin Y31 and Y118 phosphorylation in the pulmonary vasculature of chronic hypoxic mice (21 days, 10 % O2) which was reversible by imatinib-treatment. PDGF-BB-dependent PASMC proliferation was regulated via the paxillin-Erk1/2-cyclin D1 pathway. In conclusion, we suggest paxillin up-regulation and phosphorylation as an important mechanism of vascular remodelling underlying pulmonary hypertension. Free Keywords: Pulmonary arterial smooth muscle cells; cytoskeletal proteins; pulmonary hypertension; pulmonary vascular remodelling External Publication Status: published Document Type: Article Communicated by: MPI für Herz- und Lungenforschung Affiliations: MPI für physiologische und klinische Forschung External Affiliations: %^ 1435822045 Identifiers: ISSN:0340-6245 (Print) 0340-6245 (Linking) %R 10.1160/TH13-12-1031 URL:http://www.ncbi.nlm.nih.gov/pubmed/25231004 The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.