The Role of Endothelium a and Egfr Receptor in Fibrocytes from Asthma with Obstructive Sleep Apnoea (Continue)

Asthma is characterized by airflow obstruction, chronic airway inflammation andremodeling. Our previous report has shown directly the relationship between fibrocytes, andchronic airflow obstruction with rapid decline in FEV1 in asthma. Asthma concomitant ofobstructive sleep apnea (OSA) may appear intermittent hypoxia and result in the frequentattack of asthma symptoms. In animal model, hypoxia may increase the circulatingfibrocytes, thus play a role in pulmonary hypertension. Our published paper also showed thatan increased expression of EGFR, ET-AR and VEGFR in circulating fibrocytes in chronicobstructive asthmatics. It is unknown whether circulating fibrocytes from asthma with OSAhave the higher expression of EGFR, VEGFR and ET-AR compared to asthma without OSA.We are also interested in the molecular mechanism of TGF-β1 or oxidative stress involvedin the EGFR transactivation, such as Akt, PI-3K, and NF-κB pathway in circulatingfibrocytes of asthma and OSA.In this three-year project, circulating fibrocytes will be isolated from asthma and OSA tobe identified the expression of EGFR, ET-AR and VEGFR. We also investigate whetherproliferation and differentiation of fibrocytes are different between asthmatics with orwithout concomitant of OSA. We will study the correlation between the percentage ofcirculating fibrocytes and the oxygen desaturation index (ODI) and severity of sleep apneato clarify the role of hypoxia, which contributing to uncontrolled asthma. We will investigatethe signaling pathway of EGFR in fibrocytes or fibroblast. We will use microarray to studythe expression of proliferative or angiogentic genes in the fibrocytes to see any differencebetween asthma with OSA and asthma without OSA. We will also perform Proteomicsanalysis to study the different protein or gene expression of fibrocytes stimulated by TGF-β1and oxidative stress, and if so, we will study the mechanisms by which this effect may occur.This research may lead to greater focus on the treatment of airways disease, and to advancethe treatment of these diseases that is currently unsatisfactory. The results may shed light onthe new area of pathogenesis of asthma with hypoxemia, and may advance the scope oftherapy for asthma.

Project ID:PC10708-1052
External Project ID:MOST107-2314-B182-066