The Remarkable Roles of the Receptor for Advanced Glycation End Products (RAGE) and Its Soluble Isoforms in COVID-19: The Importance of RAGE Pathway in the Lung Injuries

• Published in: Indian journal of clinical biochemistry Vol. 38; no. 2; pp. 159 - 171
• Main Authors: Salehi, Mitra, Amiri, Shahin, Ilghari, Dariush, Hasham, Lawahidh Fadhil Ali, Piri, Hossein
• Format: Journal Article
• Language: English
• Published: New Delhi Springer India 01.04.2023; Springer; Springer Nature B.V
• Subjects: ACE2; Acute respiratory distress syndrome; Advanced glycosylation end products; Alveoli; Angiotensin; Angiotensin converting enzyme; Angiotensin II; Angiotensin-converting enzyme 2; Biochemistry; Biomedical and Life Sciences; Chemistry/Food Science; Chromosomal proteins; Clinical trials; Coronaviruses; COVID-19; Cytokine storm; Cytokines; Diabetes; Diabetes mellitus; Epithelial cells; Glycosylation; HMGB1 protein; Inflammatory diseases; Isoforms; Kinases; Life Sciences; Lungs; MAP kinase; Medical research; Medicine, Experimental; Microbiology; Pathology; Peptidyl-dipeptidase A; Respiratory distress syndrome; Review; Review Article; SARS-CoV- 2; Receptor for advanced glycation end products; ACE2 protein; Respiratory distress syndrome; esRAGE
• ISSN: 0970-1915; 0974-0422
• DOI: 10.1007/s12291-022-01081-5

The respiratory symptoms of acute respiratory distress syndrome (ARDS) in the coronavirus disease 2019 (COVID-19) patients is associated with accumulation of pre-inflammatory molecules such as advanced glycation end-products (AGES), calprotectin, high mobility group box family-1 (HMGB1), cytokines, angiotensin converting enzyme 2 (ACE2), and other molecules in the alveolar space of lungs and plasma. The receptor for advanced glycation end products (RAGEs), which is mediated by the mitogen-activated protein kinase (MAPK), plays a critical role in the severity of chronic inflammatory diseases such as diabetes mellitus (DM) and ARDS. The RAGE gene is most expressed in the alveolar epithelial cells (AECs) of the pulmonary system. Several clinical trials are now being conducted to determine the possible association between the levels of soluble isoforms of RAGE (sRAGE and esRAGE) and the severity of the disease in patients with ARDS and acute lung injury (ALI). In the current article, we reviewed the most recent studies on the RAGE/ligands axis and sRAGE/esRAGE levels in acute respiratory illness, with a focus on COVID-19–associated ARDS (CARDS) patients. According to the research conducted so far, sRAGE/esRAGE measurements in patients with CARDS can be used as a powerful chemical indicator among other biomarkers for assessment of early pulmonary involvement. Furthermore, inhibiting RAGE/MAPK and Angiotensin II receptor type 1 (ATR1) in CARDS patients can be a powerful strategy for diminishing cytokine storm and severe respiratory symptoms.