Title : Novel therapeutics for common and devastating chronic obstructive pulmonary disease
Abstract:
As the third leading cause of mortality in the world, chronic obstructive pulmonary disease (COPD) is a common and devastating lung disease. However, the current clinical therapeutic options for COPD are limited, and its molecular mechanisms remain largely unknown. COPD is well characterized by airway hyperresponsiveness and remodeling, thereby leading to airflow limitation. We and other well-known scientist have unveiled that a very important player (VIP) in airway hyperresponsiveness and remodeling of COPD is an increase in intracellular calcium ([Ca2+]i) in airway smooth muscle cells (AMCs). Consistent with this view, bronchodilators including muscarinic receptor antagonists, β-adrenergic receptor agonists and corticosteroids are used as the first-line drugs in the clinical treatment of COPD, and the functional role of all these forefront drugs are associated with their inhibition of the increased [Ca2+]i in ASMCs. Recent studies from our group and others suggest that multiple ion channels, particularly inositol trisphosphate receptor (IP3R)/Ca2+ release channel, ryanodine receptor (RyR)/Ca2+ release channel and canonical transient receptor potential-3 (TRPC3) channel, play a major role in initiation and maintenance of [Ca2+]i in ASMCs and thus are essential for airway hyperresponsiveness and remodeling in COPD and/or other pulmonary diseases. Equally interestingly, IP3R, RyR and TRPC3 channels are highly sensitive to reactive oxygen species (ROS), and ROS are well known to mediate airway hyperresponsiveness and/or remodeling in COPD. We have further reveal that ROS are primarily produced by mitochondria and NADPH oxidase (NOX), but mitochondria are the primary site. Several antioxidants targeted at mitochondria and/or NOX are currently used in clinical trials and show potential effectiveness in the treatment of COPD. ROS may implement their roles in COPD by causing oxidation of IP3R, RyR and TRPC3 channels, leading to their hyperfunctions. We and other eminent investigators have further provided new evidence that virus-mediated shRNA-based genetic (specific) inhibition and highly selective pharmacological inhibitor of these channels may become more effective therapies for COPD.
Audience Take-Away:
- My current presentation will greatly help the audience to create their future research directions
- The finding presented may significantly assist the audience to develop novel preventive and therapeutic strategies for COPD and other relevant pulmonary diseases
- Our research could also be used by other investigators to expand their research and/or teaching
- All my presentation may also greatly improve experimental design, implementation, data analysis, explanations, statements, and/or conclusions
