Diminished sarco/endoplasmic reticulum Ca2+ATPase (SERCA) expression contributes to airway remodelling in bronchial asthma

• DOI: 10.1073/pnas.0902295106
• Publication Date: 2009-06-17T01:50:13Z
• Authors: Katharina Mahn; Stuart J. Hirst; Sun Ying; Mark R. Holt; Paul Lavender; Oluwaseun O. Ojo; Leonard Siew; David E. Simcock; Clare G. McVicker; Varsha Kanabar; Vladimir A. Snetkov; Brian J. O'Connor; Charlotta Karner; David J. Cousins; Patricia Macedo; K. Fan Chung; Christopher J. Co...; Jeremy P. T. Ward; Tak H. Lee
• Keywords: SERCA; Thapsigargin

Phenotypic modulation of airway smooth muscle (ASM) is an important feature remodeling in asthma that characterized by enhanced proliferation and secretion pro-inflammatory chemokines. These activities are regulated the concentration free Ca(2+) cytosol ([Ca(2+)](i)). A rise [Ca(2+)](i) normalized rapid reuptake into sarcoplasmic reticulum (SR) stores sarco/endoplasmic (SERCA) pump. We examined whether increased proliferative secretory responses ASM from asthmatics result reduced SERCA expression. cells were cultured subjects with without asthma. expression was evaluated western blot, immunohistochemistry real-time PCR. Changes [Ca(2+)](i), cell spreading, cellular proliferation, eotaxin-1 release measured. Compared control healthy subjects, SERCA2 mRNA protein moderately severe similarly vivo moderate/severe Rises following surface receptor-induced SR activation, or inhibition SERCA-mediated re-uptake, attenuated asthmatics. Likewise, return to baseline [Ca](i) after stimulation bradykinin delayed approximately 50% siRNA-mediated knockdown proliferation. Our findings implicate a deficiency contributes its hyperproliferative phenotype asthma, which may play key role mechanisms remodeling.