Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Παρασκευή 8 Σεπτεμβρίου 2017

Ormdl3 Upregulates Airway Smooth Muscle Proliferation, Contraction, and Ca2+ Oscillations in Asthma

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Publication date: Available online 7 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Jun Chen, Marina Miller, Hirotoshi Unno, Peter Rosenthal, Michael Sanderson, David H. Broide
BackgroundAirway hyperresponsiveness (AHR) is a major feature of asthma attributed predominantly to an extrinsic immune/inflammatory response increasing airway smooth muscle (ASM) contractility.ObjectiveWe investigated whether increased ASM expression of ORMDL3, a gene on chromosome 17q21 highly linked to asthma, induced increased ASM proliferation and contractility in vitro, as well as influenced airway contractility and calcium flux in ASM in precision cut lung slices from WT and hORMDL3Zp3-Cre mice (which express increased levels of human ORMDL3).MethodsLevels of ASM proliferation and contraction were assessed in ASM cells transfected with ORMDL3 in vitro. In addition, airway contractility and calcium oscillations were quantitated in ASM cells in precision cut lung slices derived from naïve WT and naïve hORMDL3Zp3-Cre mice which do not have a blood supply.ResultsIncreased ASM expression of ORMDL3 in vitro resulted in increased ASM proliferation and contractility. Precision cut lung slices derived from naïve hORMDL3Zp3-Cre mice which do not have airway inflammation exhibit increased airway contractility with increased calcium oscillations in ASM cells. Increased ASM ORMDL3 increases ASM sarcoplasmic reticulum Ca2+ ATPase 2b (SERCA2b) which increases ASM proliferation and contractility.ConclusionOverall, these studies provide evidence that an intrinsic increase in ORMDL3 in ASM can induce increased ASM proliferation and contractility which may contribute to increased AHR in the absence of airway inflammation in asthma.

Teaser

This study demonstrates that an intrinsic increase in ORMDL3 in ASM can induce increased ASM proliferation and contractility which might contribute to increased AHR in the absence of airway inflammation in asthma.


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