Biography
Biography: Jamila Chakir
Abstract
Allergic asthma is a chronic inflammatory disease characterized by an airway hyper-responsiveness and a deregulated inflammation in response to allergens. Available treatments are mainly symptoms-driven and do not interfere with the natural history of the diseases. Severe asthma constitutes a challenging problem for the healthcare system. Its heterogeneity complicates the management of the disease. There is a significant need to understand the pathogenesis of severe asthma. Bronchial epithelium is considered a key player in coordinating airway wall remodelling. While, in mild asthma, the epithelium is damaged and fails to proliferate and to repair in severe asthma the epithelium was reported to be highly proliferative and thicker. This may be due to different regulatory mechanisms. We studied microRNAs profile and evaluated their role in regulating proliferation of bronchial epithelial cells obtained from severe asthmatic subjects in comparison to cells obtained from mild asthmatics and healthy controls. We found that in mild asthmaepithelial cells produce high amount of TGFï¢1 and express high level of TGFï¢-RI and phosphorylated-Smad3, indicating that TGFï¢1signallingis up-regulated. In severe asthma, this pathway was down-regulated. Thus, in epithelial cells from severe asthmatics compared to mild asthma and controls, miR-19a, a member of the miR-17~92 cluster, is up-regulated and increases proliferation. Knockdown of miR-19a in epithelial cells reduces significantly their proliferation through targeting TGF-ï¢ downstream signaling. Our study uncovers a new regulatory pathway involving miR-19a that is critical to the severe phenotype of asthma and indicates that down-regulating miR-19a expression could be explored as a potential new therapy to modulate theepithelium repair in asthma (Funded by the CIHR).