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

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Abstract

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.

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Acknowledgements

AS and SK are thankful to the Jaypee University of Information Technology, Solan, Himachal Pradesh, India, for the Junior Research Fellowship. An apology is due to the researchers for not citing their contribution in the field due to space limitations.

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  1. Ambika Sharma and Sargeet Kaur contributed equally to this work.

Authors and Affiliations

  1. Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, 173 234, India

    Ambika Sharma, Sargeet Kaur & Harish Changotra

  2. Department of Pulmonary Medicine, Indira Gandhi Medical College, Shimla, Himachal Pradesh, 171 001, India

    Malay Sarkar

  3. Department of Chest and TB, Sri Guru Ram Das Institute of Medical Sciences and Research, Vallah, Amritsar, 143 501, India

    B. C. Sarin

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AS and SK performed the literature survey and wrote the first draft and following revisions of the manuscript. MS and BCS participated in the manuscript writing and reviewed the manuscript. HC participated in the manuscript writing, reviewed and edited the manuscript and approved the final version of the manuscript.

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Sharma, A., Kaur, S., Sarkar, M. et al. The AGE-RAGE Axis and RAGE Genetics in Chronic Obstructive Pulmonary Disease. Clinic Rev Allerg Immunol 60, 244–258 (2021). https://doi.org/10.1007/s12016-020-08815-4

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