Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Biasin, V; Chwalek, K; Wilhelm, J; Best, J; Marsh, LM; Ghanim, B; Klepetko, W; Fink, L; Schermuly, RT; Weissmann, N; Olschewski, A; Kwapiszewska, G.
Endothelin-1 driven proliferation of pulmonary arterial smooth muscle cells is c-fos dependent.
Int J Biochem Cell Biol. 2014; 54(3):137-148
Doi: 10.1016/j.biocel.2014.06.020
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Biasin Valentina
- Kwapiszewska-Marsh Grazyna
- Co-Autor*innen der Med Uni Graz
- Marsh Leigh
- Olschewski Andrea
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Pulmonary hypertension (PH) is characterized by enhanced pulmonary artery smooth muscle cell (PASMC) proliferation leading to vascular remodeling. Although, multiple factors have been associated with pathogenesis of PH the underlying mechanisms are not fully understood. Here, we hypothesize that already very short exposure to hypoxia may activate molecular cascades leading to vascular remodeling. Microarray studies from lung homogenates of mice exposed to only 3h of hypoxia revealed endothelin-1 (ET-1) and connective tissue growth factor (CTGF) as the most upregulated genes, and the mitogen-activated protein kinase (MAPK) pathway as the most differentially regulated pathway. Evaluation of these results in vitro showed that ET-1 but not CTGF stimulation of human PASMCs increased DNA synthesis and expression of proliferation markers such as Ki67 and cell cycle regulator, cyclin D1. Moreover, ET-1 treatment elevated extracellular signal-regulated kinase (Erk)-dependent c-fos expression and phosphorylation of c-fos and c-jun transcription factors. Silencing of c-fos with siRNA abrogated the ET-1-induced proliferation of PASMCs. Expression and immunohistochemical analyses revealed higher levels of total and phosphorylated c-fos and c-jun in the vessel wall of lung samples of human idiopathic pulmonary arterial hypertension patents, hypoxia-exposed mice and monocrotaline-treated rats as compared to control subjects. These findings shed the light on the involvement of c-fos/c-jun in the proliferative response of PASMCs to ET-1 indicating that already very short hypoxia exposure leads to the regulation of mediators involved in vascular remodeling underlying PH. Copyright © 2014 Elsevier Ltd. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apoptosis -
- Biomarkers - metabolism
- Blotting, Western -
- Case-Control Studies -
- Cell Proliferation -
- Cells, Cultured -
- Endothelin-1 - pharmacology
- Extracellular Signal-Regulated MAP Kinases - genetics
- Extracellular Signal-Regulated MAP Kinases - metabolism
- Familial Primary Pulmonary Hypertension - drug therapy
- Familial Primary Pulmonary Hypertension - metabolism
- Familial Primary Pulmonary Hypertension - pathology
- Fluorescent Antibody Technique -
- Gene Expression Profiling -
- Humans -
- Hypoxia - genetics
- Hypoxia - metabolism
- Hypoxia - pathology
- Immunoenzyme Techniques -
- Lung - cytology
- Lung - drug effects
- Lung - metabolism
- Male -
- Mice -
- Mice, Inbred BALB C -
- Mice, Inbred C57BL -
- Mitogen-Activated Protein Kinases - genetics
- Mitogen-Activated Protein Kinases - metabolism
- Muscle, Smooth, Vascular - cytology
- Muscle, Smooth, Vascular - drug effects
- Muscle, Smooth, Vascular - metabolism
- Oligonucleotide Array Sequence Analysis -
- Phosphorylation -
- Proto-Oncogene Proteins c-fos - genetics
- Proto-Oncogene Proteins c-fos - metabolism
- Pulmonary Artery - cytology
- Pulmonary Artery - drug effects
- Pulmonary Artery - metabolism
- RNA, Messenger - genetics
- Rats -
- Rats, Sprague-Dawley -
- Real-Time Polymerase Chain Reaction -
- Reverse Transcriptase Polymerase Chain Reaction -
- Signal Transduction -
- Find related publications in this database (Keywords)
- Pulmonary hypertension
- Proliferation
- Endothelin-1
- Transcription factor
- c-Fos