例如:"lncRNA", "apoptosis", "WRKY"

Dysregulation of the IL-13 receptor system: a novel pathomechanism in pulmonary arterial hypertension.

Am. J. Respir. Crit. Care Med.2010 Sep 15;182(6):805-18. Epub 2010 Jun 03
Matthias Hecker 1 , Zbigniew Zaslona , Grazyna Kwapiszewska , Gero Niess , Anna Zakrzewicz , Eduard Hergenreider , Jochen Wilhelm , Leigh M Marsh , Daniel Sedding , Walter Klepetko , Jürgen Lohmeyer , Stefanie Dimmeler , Werner Seeger , Norbert Weissmann , Ralph T Schermuly , Nikolaus Kneidinger , Oliver Eickelberg , Rory E Morty
Matthias Hecker 1 , Zbigniew Zaslona , Grazyna Kwapiszewska , Gero Niess , Anna Zakrzewicz , Eduard Hergenreider , Jochen Wilhelm , Leigh M Marsh , Daniel Sedding , Walter Klepetko , Jürgen Lohmeyer , Stefanie Dimmeler , Werner Seeger , Norbert Weissmann , Ralph T Schermuly , Nikolaus Kneidinger , Oliver Eickelberg , Rory E Morty
+ et al

[No authors listed]

Author information
  • 1 Department of Internal Medicine (Pulmonology), University of Giessen Lung Center, Justus Liebig University, Giessen, Germany.

摘要


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-13Rα1, and IL-13Rα2 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-13Rα2 was up-regulated relative to that of the IL-13 signaling receptors IL-4R and IL-13Rα1 in patients with IPAH and in two animal models of IPAH. IL-13, signaling via and 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.