Document Detail


Airway smooth muscle STIM1 and Orai1 are upregulated in asthmatic mice and mediate PDGF-activated SOCE, CRAC currents, proliferation, and migration.
MedLine Citation:
PMID:  23014880     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Amy M Spinelli; José C González-Cobos; Xuexin Zhang; Rajender K Motiani; Sarah Rowan; Wei Zhang; Joshua Garrett; Peter A Vincent; Khalid Matrougui; Harold A Singer; Mohamed Trebak
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-09-27
Journal Detail:
Title:  Pflügers Archiv : European journal of physiology     Volume:  464     ISSN:  1432-2013     ISO Abbreviation:  Pflugers Arch.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-15     Completed Date:  2013-02-18     Revised Date:  2013-12-06    
Medline Journal Info:
Nlm Unique ID:  0154720     Medline TA:  Pflugers Arch     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  481-92     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Asthma / chemically induced,  metabolism*,  physiopathology*
Calcium / metabolism
Calcium Channels / genetics,  metabolism*
Calcium Signaling*
Cell Movement
Cell Proliferation
Disease Models, Animal
Male
Membrane Glycoproteins / genetics,  metabolism*
Membrane Potentials
Mice
Mice, Inbred C57BL
Myocytes, Smooth Muscle / metabolism,  physiology*
Platelet-Derived Growth Factor / pharmacology*
RNA, Small Interfering
Rats
Rats, Sprague-Dawley
Trachea / cytology
Up-Regulation
Grant Support
ID/Acronym/Agency:
HL095566/HL/NHLBI NIH HHS; HL097111/HL/NHLBI NIH HHS; R01 HL049426/HL/NHLBI NIH HHS; R01 HL092510/HL/NHLBI NIH HHS; R01 HL095566/HL/NHLBI NIH HHS; R01 HL097111/HL/NHLBI NIH HHS; R01HL49426/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Calcium Channels; 0/Membrane Glycoproteins; 0/Orai1 protein, mouse; 0/Platelet-Derived Growth Factor; 0/RNA, Small Interfering; 0/Stim1 protein, mouse; SY7Q814VUP/Calcium
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Molecular systems for light driven hydrogen production.
Next Document:  The limitations of renal epithelial cell line HK-2 as a model of drug transporter expression and fun...