The AGE-RAGE Axis and RAGE Genetics in Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of lung diseases limiting the airflow due to narrowing of airways, chronic bronchitis and emphysema that leads to difficulties in breathing. Chronic inflammation is another important characteristic of COPD which leads to immune cell infiltration and helps in the alveolar destruction. Pathology of COPD is driven by various environmental and genetic factors. COPD is mainly associated with the inhalation of toxic agents mainly the cigarette smoke. Receptor for advanced glycation end products (RAGE) has emerged as a pattern recognition receptor and is a multiligand receptor expressed moderately in various cells, tissues and highly in the lungs throughout life. RAGE recognizes various ligands produced by cigarette smoke and its role has been implicated in the pathogenesis of COPD. RAGE ligands have been reported to accumulate in the lungs of patients with COPD. RAGE is a membrane receptor but its truncated form i.e. soluble RAGE (sRAGE) mainly functions as a contender of RAGE and inhibits various RAGE dependent cell signalling. Among the various ligands of RAGE, advanced glycation end products (AGEs) are majorly linked with COPD. Accumulated AGE triggers downstream RAGE-AGE axis in COPD. Moreover, RAGE genetics has long been known to play a vital role in the pathology of various airway diseases including COPD and this gene contains an associated locus. A reliable biomarker is needed for the management of this disease. sRAGE has an inverse correlation with the RAGE showed its importance as a valuable marker in COPD. This review is focused on the role of RAGE, sRAGE, RAGE axis and RAGE genetics in COPD.