Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hecker, M; Zaslona, Z; Kwapiszewska, G; Niess, G; Zakrzewicz, A; Hergenreider, E; Wilhelm, J; Marsh, LM; Sedding, D; Klepetko, W; Lohmeyer, J; Dimmeler, S; Seeger, W; Weissmann, N; Schermuly, RT; Kneidinger, N; Eickelberg, O; Morty, RE.
Dysregulation of the IL-13 receptor system: a novel pathomechanism in pulmonary arterial hypertension.
Am J Respir Crit Care Med. 2010; 182(6): 805-818.
Doi: 10.1164/rccm.200909-1367OC
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Kwapiszewska-Marsh Grazyna
- Marsh Leigh
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- RATIONALE: Idiopathic pulmonary arterial hypertension (IPAH) is characterized by medial hypertrophy due to pulmonary artery smooth muscle cell (paSMC) hyperplasia. Inflammation is proposed to play a role in vessel remodeling associated with IPAH. IL-13 is emerging as a regulator of tissue remodeling; however, the contribution of the IL-13 system to IPAH has not been assessed. OBJECTIVES: The objective of this study was to assess the possible contribution of the IL-13 system to IPAH. METHODS: Expression and localization of IL-13, and IL-13 receptors IL-4R, IL-13Ra1, and IL-13Ra2 were assessed by real-time reverse transcription-polymerase chain reaction, immunohistochemistry, and flow cytometry in lung tissue, paSMC, and microdissected vascular lesions from patients with IPAH, and in lung tissue from rodents with hypoxia- or monocrotaline-induced pulmonary hypertension. A whole-genome microarray analysis was used to study IL-13-regulated genes in paSMC. MEASUREMENTS AND MAIN RESULTS: Pulmonary expression of the IL-13 decoy receptor IL-13Ra2 was up-regulated relative to that of the IL-13 signaling receptors IL-4R and IL-13Ra1 in patients with IPAH and in two animal models of IPAH. IL-13, signaling via STAT3 and STAT6, suppressed proliferation of paSMC by promoting G(0)/G(1) arrest. Whole-genome microarrays revealed that IL-13 suppressed endothelin-1 production by paSMC, suggesting that IL-13 controlled paSMC growth by regulating endothelin production. Ectopic expression of the il13ra2 gene resulted in partial loss of paSMC growth control by IL-13 and blunted IL-13 suppression of endothelin-1 production by paSMC, whereas small-interfering RNA knockdown of il13ra2 gene expression had the opposite effects. CONCLUSIONS: The IL-13 system is a novel regulator of paSMC growth. Dysregulation of IL-13 receptor expression in IPAH may partially underlie smooth muscle hypertrophy associated with pathological vascular remodeling in IPAH.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Animals -
- Disease Models, Animal -
- Female -
- Flow Cytometry -
- Humans -
- Hypertension, Pulmonary - etiology
- Immunohistochemistry -
- Interleukin-13 - metabolism
- Interleukin-13 Receptor alpha1 Subunit - metabolism
- Interleukin-13 Receptor alpha2 Subunit - metabolism
- Lung - metabolism
- Male -
- Mice -
- Middle Aged -
- Muscle, Smooth, Vascular - metabolism
- Myocytes, Smooth Muscle - metabolism
- Pulmonary Artery - metabolism
- Rats -
- Receptors, Interleukin-13 - physiology
- Reverse Transcriptase Polymerase Chain Reaction -
- Up-Regulation - physiology
- Young Adult -
- Find related publications in this database (Keywords)
- smooth muscle
- endothelin
- interleukin
- pulmonary arterial hypertension