Receptor for Advanced Glycation End Products in Pulmonary Diseases

The receptor for advanced glycation end products (RAGE) is characterized as a multi-ligand pattern recognition receptor molecule exhibiting physiologically profuse expression in the lung alveolar type 1 (AT-1) epithelial cell’s basolateral region. Advanced glycation end products (AGEs) are the most prominent among the multiple ligands of RAGE in lung tissues. Other major RAGE ligands comprise high mobility group box protein 1 (HMGB-1) and S100/calgranulin. In various pathophysiological conditions, lung tissues express the supraphysiological level of RAGE and its multiple ligands. In physiological conditions, the interaction of RAGE with its ligands assists in the maturity, spreading, and maintenance-enabled homeostasis of lung epithelial cells. Thus, physiologically abundant expression of RAGE in the lung AT-1 cells maintains their morphology and specific architecture. In physiological conditions, high basal level expression of RAGE in the lung tissues guards against the development of non-small cell lung cancers (NSCLCs), wherein decreased RAGE extents are correlated with non-small cell lung cancer (NSCLC) complications. However, in the lung tissues under pathophysiological conditions, supraphysiological expression of RAGE and its various ligands stimulates inflammation and oxidative stress-related cell signaling molecules. This aggravated extent of inflammation and oxidative stress in the lung tissues leads to the propagation of manifold lung diseases namely, asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and cystic fibrosis (CF), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), pneumonia, sepsis, bronchopulmonary dysplasia, and pulmonary hypertension. This chapter describes the physiological and pathophysiological role of RAGE in the lungs and the anti-RAGE therapy against various lung diseases.