The receptor for advanced glycation end product (RAGE) pathway in COVID-19

Kehribar, Demet Yalçın; Cihangiroğlu, Mustafa; Sehmen, Emine; Avcı, Bahattin; Çapraz, Aylin; Bilgin, Ayse Yildirim; Günaydın, Caner; Özgen, Metin

doi:10.1080/1354750x.2020.1861099

Cited by 46 publications

(34 citation statements)

References 31 publications

(37 reference statements)

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“…However, the association of sRAGE plasma levels with the severity of COVID-19 is controversial. Although a study reported that asymptomatic COVID-19 patients showed higher serum levels of sRAGE than patients with lung involvement [79], others found that significantly higher plasma levels of sRAGE characterized COVID-19-associated ARDS compared with non-COVID-19associated ARDS, and that plasma levels of sRAGE were associated with disease severity, the need for mechanical ventilation, and mortality in COVID-19 [124,125].…”

Section: Concluding Remarks and Perspectivesmentioning

confidence: 97%

“…The potential key role of RAGE in the severe forms of COVID-19 is highlighted by very recent findings about some of its ligands: (i) serum levels of AGEs were found to be higher in COVID-19 patients with lung involvement than in asymptomatic patients [79]; (ii) S100A12 was found to be one of the differentially expressed proteins in the bronchoalveolar lavage fluid of critical COVID-19 patients [80]; (iii) elevated levels of S100B and S100A8/A9 were detected in the serum of COVID-19 patients, significantly correlating with the severity of disease [81,82]; and (iv) the serum levels of S100A8/A9 and HMGB1 at hospital admission were found to be increased in intensive care unit (ICU) compared to non-ICU patients, and in fatal outcomes compared to surviving patients, in a retrospective study of COVID-19 patients [83]. Altogether, these data indicate that S100A12 is involved in COVID-19 lung tissue damage, and that the elevation of AGEs S100B, S100A8/A9, and HMGB1 in the serum of SARS-CoV-2-infected people is associated with worse outcomes and increased mortality, pointing to an overall convergence of RAGE signaling in severe COVID-19.…”

Section: Rage In Severe Covid-19mentioning

confidence: 99%

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Hyperactivated RAGE in Comorbidities as a Risk Factor for Severe COVID-19—The Role of RAGE-RAS Crosstalk

et al. 2021

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The receptor for advanced glycation-end products (RAGE) is a multiligand receptor with a role in inflammatory and pulmonary pathologies. Hyperactivation of RAGE by its ligands has been reported to sustain inflammation and oxidative stress in common comorbidities of severe COVID-19. RAGE is essential to the deleterious effects of the renin–angiotensin system (RAS), which participates in infection and multiorgan injury in COVID-19 patients. Thus, RAGE might be a major player in severe COVID-19, and appears to be a useful therapeutic molecular target in infections by SARS-CoV-2. The role of RAGE gene polymorphisms in predisposing patients to severe COVID-19 is discussed.

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Section: Concluding Remarks and Perspectivesmentioning

confidence: 97%

Section: Rage In Severe Covid-19mentioning

confidence: 99%

Hyperactivated RAGE in Comorbidities as a Risk Factor for Severe COVID-19—The Role of RAGE-RAS Crosstalk

et al. 2021

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“…The RAGE pathway is mainly expressed in lung tissue and linked to development of acute and chronic lung injuries (59). In Covid-19, SARS-CoV-2 activates mRAGE at pulmonary alveolar cells leading to induction of severe inflammatory reactions (60). Indeed, it has been reported that sRAGE concentration is reduced with aging, which might explain the susceptibility of the elderly to Covid-19.…”

Section: Estrogen and Signaling Pathway In Covid-19mentioning

confidence: 99%

The Looming Effects of Estrogen in Covid-19: A Rocky Rollout

et al. 2021

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In the face of the Covid-19 pandemic, an intensive number of studies have been performed to understand in a deeper way the mechanisms behind better or worse clinical outcomes. Epidemiologically, men subjects are more prone to severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) infections than women, with a similar scenario being also stated to the previous coronavirus diseases, namely, SARS-CoV in 2003 and Middle East Respiratory Syndrome coronavirus diseases (MERS-CoV) in 2012. In addition, and despite that aging is regarded as an independent risk factor for the severe form of the disease, even so, women protection is evident. In this way, it has been expected that sex hormones are the main determinant factors in gender differences, with the immunomodulatory effects of estrogen in different viral infections, chiefly in Covid-19, attracting more attention as it might explain the case-fatality rate and predisposition of men for Covid-19 severity. Here, we aim to provide a mini-review and an overview on the protective effects of estrogen in Covid-19. Different search strategies were performed including Scopus, Web of Science, Medline, Pubmed, and Google Scholar database to find relative studies. Findings of the present study illustrated that women have a powerful immunomodulating effect against Covid-19 through the effect of estrogen. This study illustrates that estrogens have noteworthy anti-inflammatory and immuno-modulatory effects in Covid-19. Also, estrogen hormone reduces SARS-CoV-2 infectivity through modulation of pro-inflammatory signaling pathways. This study highlighted the potential protective effect of estrogen against Covid-19 and recommended for future clinical trial and prospective studies to elucidate and confirm this protective effect.

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“…The colonic expression of RAGE and some RAGE ligands, such as HMGB1 and some members of the S100 protein family, are significantly higher in IBD patients[ 54 - 56 ]. Besides, this receptor has been also considered a key contributor to the dysregulated and misdirected COVID-19 inflammatory response[ 32 , 94 ].…”

Section: Rage Axis Activation and Ras Imbalance In Ibd Patients Infected With Sars-cov-2mentioning

confidence: 99%

“…A compelling body of both clinical and experimental evidence has shed light on the crucial role of the receptor of advanced glycation end-products (RAGE) activation in many chronic inflammatory diseases[ 26 - 31 ]. More recently, the role of RAGE axis activation as a key contributor in the clinical course of SARS-CoV-2 infection has been documented[ 32 ].…”

Section: Introductionmentioning

confidence: 99%

Receptor for advanced glycation end-products axis and coronavirus disease 2019 in inflammatory bowel diseases: A dangerous liaison?

Rojas

Schneider

Lindner

et al. 2021

WJG

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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.

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The receptor for advanced glycation end product (RAGE) pathway in COVID-19

Cited by 46 publications

References 31 publications

Hyperactivated RAGE in Comorbidities as a Risk Factor for Severe COVID-19—The Role of RAGE-RAS Crosstalk

Hyperactivated RAGE in Comorbidities as a Risk Factor for Severe COVID-19—The Role of RAGE-RAS Crosstalk

The Looming Effects of Estrogen in Covid-19: A Rocky Rollout

Receptor for advanced glycation end-products axis and coronavirus disease 2019 in inflammatory bowel diseases: A dangerous liaison?

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