Study on the Mechanism of Cross-Talk between Ahr and Autophagy, and Autophagy---Associated Physiological or Pathological Phenomenon on Vascular and Airway Systems (I)

Autophagy represents a protective function, which accelerated abnormal protein degradation, removed exogenous pathogens and mediated cellular/physiological homeostasis. Growing evidences indicate that autophagy dysfunctions may results in angiogenesis, airway inflammation, fibrosis, diabetes-mediated nephritis, malignant tumor, and neurodegenerative diseases, in biphasic manners. In patients of cardiovascular and respiratory diseases, their symptoms become worse when expose to polycyclic aromatic hydrocarbons (PAHs), the ligands of aryl hydrocarbon receptor (AhR). That means the AhR transactivation pathway may involve in the pathogenesis of cardiovascular and respiratory diseases. Previously, we found benzo[a]pyrene (B[a]P), a typical AhR ligand, induce autophagy in both endothelial and epithelial cells. As we known, autophagy usually prevents endothelial cell from apoptosis, but enhances angiogenesis. Yet, B[a]P treatment either causes AhR degradation or inhibits angiogenesis in vitro. Take these findings together, we propose a cross-talk signaling may exist between AhR and autophagy. To find out the detailed mechanism, the 3-year research program has been proposed. Firstly, by using epithelial and endothelial cell testing models, the molecular interaction or cross-talk factors involved in AhR and autophagy signaling will be studied. With connections to sub-program I (the relationship between AhR and EnMT-related phenotypic performances) and sub-program II (the relationship between AhR and EMT-related phenotypic performances), the AhR-dependent regulation on autophagy-mediated vascular remodeling, fibrosis and neovascularization, and autophagy-mediated airway inflammation, remodeling and fibrosis will be clarified, respectively. The biological samples provided from other sub-programs will be helpful to autophagy identification in our study. The AhR-regulated autophagy epigenetic changes may be an atypical pathway, either in physiological or pathological function. Understanding the basis of AhR/autophagy cross-talking also provides a novel therapeutic strategy in the future.