Store-operated calcium entry-associated regulatory factor regulates airway inflammation and airway remodeling in asthma mice models
- 1 September 2021
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Lung Cellular and Molecular Physiology
- Vol. 321 (3), L533-L544
- https://doi.org/10.1152/ajplung.00079.2020
Abstract
Background: Store-operated calcium entry (SOCE) is involved in the pathogenesis of airway inflammation and remodeling in asthma. Store-operated calcium entry-associated regulatory factor (SARAF) can down-regulate SOCE. Objective: We sought to investigate the role of SARAF in the regulation of airway inflammation and remodeling in asthma mice models, as well as in the functional regulation of human airway smooth muscle cells (hASMCs). Methods: Balb/c mice were sensitized and challenged with ovalbumin to establish the asthma mice models. Mice were transfected with lentivirus, which expressed the SARAF gene + GFP or the negative control gene + GFP. Airway resistance was measured with the animal pulmonary function system. Airway inflammation and remodeling were evaluated via histological staining. In vitro cultured hASMCs were transfected with scrambled small interfering RNA(siRNA) or SARAF-specific siRNA respecitvely. The proliferation, migration rate, hypertrophy and SOCE activity of hASMCs were examined with cell counting kit 8, wound healing test, bright field imaging and Ca2+ fluorescence imaging, respectively. SARAF expression was measured by quantitative real-time-PCR. Results: Asthma mice models showed decreased SARAF mRNA expression in the lungs. SARAF overexpression attenuated airway inflammation, resistance and also remodeling. Downregulation of SARAF expression with siRNA promoted the proliferation, migration, hypertrophy and SOCE activity in hASMCs. Conclusions: SARAF plays a protective role against airway inflammation and remodeling in asthma mice models by blunting SOCE; SARAF may also be a functional regulating factor of hASMCs.Keywords
Funding Information
- Zhongnan Hospital of Wuhan University (znpy 2018110)
This publication has 57 references indexed in Scilit:
- Airway smooth muscle pathophysiology in asthmaJournal of Allergy and Clinical Immunology, 2021
- Store-operated Ca2+ entry in primary murine lung fibroblasts is independent of classical transient receptor potential (TRPC) channels and contributes to cell migrationScientific Reports, 2020
- AsthmaAllergy, Asthma & Clinical Immunology, 2018
- Overexpression of SARAF Ameliorates Pressure Overload–Induced Cardiac Hypertrophy Through Suppressing STIM1-Orai1 in MiceCellular Physiology and Biochemistry, 2018
- AsthmaThe Lancet, 2018
- Chinese guidelines for childhood asthma 2016: Major updates, recommendations and key regional dataJournal of Asthma, 2017
- Store‐operated calcium entry is required for sustained contraction and Ca2+ oscillations of airway smooth muscleJournal Of Physiology-London, 2016
- Airway smooth muscle in asthma: Linking contraction and mechanotransduction to disease pathogenesis and remodellingPulmonary Pharmacology & Therapeutics, 2014
- Reverse mode Na+/Ca2+ exchange mediated by STIM1 contributes to Ca2+ influx in airway smooth muscle following agonist stimulationRespiratory Research, 2010
- Human Airway Contraction and Formoterol-Induced Relaxation Is Determined by Ca2+ Oscillations and Ca2+ SensitivityAmerican Journal of Respiratory Cell and Molecular Biology, 2010