Published online May 21, 2021. doi: 10.3748/wjg.v27.i19.2270
Peer-review started: January 24, 2021
First decision: February 22, 2021
Revised: February 22, 2021
Accepted: April 13, 2021
Article in press: April 13, 2021
Published online: May 21, 2021
Compelling evidence supports the crucial role of the receptor for advanced glycation end-products (RAGE) axis activation in many clinical entities. Since the beginning of the coronavirus disease 2019 pandemic, there is an increasing concern about the risk and handling of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in inflammatory gastrointestinal disorders, such as inflammatory bowel diseases (IBD). However, clinical data raised during pandemic suggests that IBD patients do not have an increased risk of contracting SARS-CoV-2 infection or develop a more severe course of infection. In the present review, we intend to highlight how two potentially important contributors to the inflammatory response to SARS-CoV-2 infection in IBD patients, the RAGE axis activation as well as the cross-talk with the renin-angiotensin system, are dampened by the high expression of soluble forms of both RAGE and the angiotensin-converting enzyme (ACE) 2. The soluble form of RAGE functions as a decoy for its ligands, and soluble ACE2 seems to be an additionally attenuating contributor to RAGE axis activation, particularly by avoiding the transactivation of the RAGE axis that can be produced by the virus-mediated imbalance of the ACE/angiotensin II/angiotensin II receptor type 1 pathway.
Core Tip: Data raised during the pandemic suggest that inflammatory bowel diseases do not have an increased risk of contracting severe acute respiratory syndrome coronavirus 2 infection or develop a more severe course of infection. These findings are in some way unexpected considering that inflammatory bowel disease is a chronic inflammatory state of the gastrointestinal tract. We herein discuss how the receptor for advanced glycation end-products axis activation as well as the cross-talk with the renin-angiotensin system are dampened by the high expression of soluble forms of both receptor for advanced glycation end-products and angiotensin-converting enzyme 2.