Article
Resolution of allergic airways inflammation but persistence of airway smooth muscle proliferation after repeated allergen exposures.
Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, UK.
Clinical & Experimental Allergy (impact factor:
5.03).
03/2004;
34(2):213-20.
Source: PubMed
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Citations (0)
- Cited In (2)
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Article: Airway smooth muscle growth in asthma: proliferation, hypertrophy, and migration.
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ABSTRACT: Increased airway smooth muscle mass is present in fatal and non-fatal asthma. However, little information is available regarding the cellular mechanism (i.e., hyperplasia vs. hypertrophy). Even less information exists regarding the functional consequences of airway smooth muscle remodeling. It would appear that increased airway smooth muscle mass would tend to increase airway narrowing and airflow obstruction. However, the precise effects of increased airway smooth muscle mass on airway narrowing are not known. This review will consider the evidence for airway smooth muscle cell proliferation and hypertrophy in asthma, potential functional effects, and biochemical mechanisms.Proceedings of the American Thoracic Society 02/2008; 5(1):89-96. -
Article: Airway smooth muscle STIM1 and Orai1 are upregulated in asthmatic mice and mediate PDGF-activated SOCE, CRAC currents, proliferation, and migration.
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ABSTRACT: Airway smooth muscle cell (ASMC) remodeling contributes to the structural changes in the airways that are central to the clinical manifestations of asthma. Ca(2+) signals play an important role in ASMC remodeling through control of ASMC migration and hypertrophy/proliferation. Upregulation of STIM1 and Orai1 proteins, the molecular components of the store-operated Ca(2+) entry (SOCE) pathway, has recently emerged as an important mediator of vascular remodeling. However, the potential upregulation of STIM1 and Orai1 in asthmatic airways remains unknown. An important smooth muscle migratory agonist with major contributions to ASMC remodeling is the platelet-derived growth factor (PDGF). Nevertheless, the Ca(2+) entry route activated by PDGF in ASMC remains elusive. Here, we show that STIM1 and Orai1 protein levels are greatly upregulated in ASMC isolated from ovalbumin-challenged asthmatic mice, compared to control mice. Furthermore, we show that PDGF activates a Ca(2+) entry pathway in rat primary ASMC that is pharmacologically reminiscent of SOCE. Molecular knockdown of STIM1 and Orai1 proteins inhibited PDGF-activated Ca(2+) entry in these cells. Whole-cell patch clamp recordings revealed the activation of Ca(2+) release-activated Ca(2+) (CRAC) current by PDGF in ASMC. These CRAC currents were abrogated upon either STIM1 or Orai1 knockdown. We show that either STIM1 or Orai1 knockdown significantly inhibited ASMC proliferation and chemotactic migration in response to PDGF. These results implicate STIM1 and Orai1 in PDGF-induced ASMC proliferation and migration and suggest the potential use of STIM1 and Orai1 as targets for ASMC remodeling during asthma.Pflügers Archiv - European Journal of Physiology 09/2012; 464(5):481-92. · 4.46 Impact Factor
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Keywords
1 week
7 days
airway inflammation
ASM cell proliferation
asthmatic airways
bronchial hyper-responsiveness
bronchial inflammation
bronchial responsiveness
bronchial submucosa
bronchoalveolar lavage
CD2+ T cells
cellular infiltration
characteristic airway smooth muscle
Chronic inflammation
major basic protein
OVA-exposed rats
OVA-specific serum IgE
Repeated OVA-challenge results
saline aerosol
third day