RAGE signalling in obesity and diabetes: focus on the adipose tissue macrophage

Feng, Ziqian; Zhu, Luochen; Wu, Jianbo

doi:10.1080/21623945.2020.1817278

Cited by 22 publications

(16 citation statements)

References 25 publications

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“…Moreover, inflammatory macrophages disrupt ECM homeostasis, which leads to fibrosis (2). Lastly, advanced glycation end-products (AGE) that are increased in obese diabetic patients, impact both adipocyte and immune cells functions, as both cell types express the receptor for AGE (RAGE) (73,74). On the whole, inflammation in AT is triggered by several integrated mechanisms and involves the various cell subsets in the AT, i.e.…”

Section: Immune System Activation and Inflammatory Activity Of At In Obese Contextsmentioning

confidence: 99%

Contribution of Adipose Tissue to the Chronic Immune Activation and Inflammation Associated With HIV Infection and Its Treatment

et al. 2021

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White adipose tissue (AT) contributes significantly to inflammation – especially in the context of obesity. Several of AT’s intrinsic features favor its key role in local and systemic inflammation: (i) large distribution throughout the body, (ii) major endocrine activity, and (iii) presence of metabolic and immune cells in close proximity. In obesity, the concomitant pro-inflammatory signals produced by immune cells, adipocytes and adipose stem cells help to drive local inflammation in a vicious circle. Although the secretion of adipokines by AT is a prime contributor to systemic inflammation, the lipotoxicity associated with AT dysfunction might also be involved and could affect distant organs. In HIV-infected patients, the AT is targeted by both HIV infection and antiretroviral therapy (ART). During the primary phase of infection, the virus targets AT directly (by infecting AT CD4 T cells) and indirectly (via viral protein release, inflammatory signals, and gut disruption). The initiation of ART drastically changes the picture: ART reduces viral load, restores (at least partially) the CD4 T cell count, and dampens inflammatory processes on the whole-body level but also within the AT. However, ART induces AT dysfunction and metabolic side effects, which are highly dependent on the individual molecules and the combination used. First generation thymidine reverse transcriptase inhibitors predominantly target mitochondrial DNA and induce oxidative stress and adipocyte death. Protease inhibitors predominantly affect metabolic pathways (affecting adipogenesis and adipocyte homeostasis) resulting in insulin resistance. Recently marketed integrase strand transfer inhibitors induce both adipocyte adipogenesis, hypertrophy and fibrosis. It is challenging to distinguish between the respective effects of viral persistence, persistent immune defects and ART toxicity on the inflammatory profile present in ART-controlled HIV-infected patients. The host metabolic status, the size of the pre-established viral reservoir, the quality of the immune restoration, and the natural ageing with associated comorbidities may mitigate and/or reinforce the contribution of antiretrovirals (ARVs) toxicity to the development of low-grade inflammation in HIV-infected patients. Protecting AT functions appears highly relevant in ART-controlled HIV-infected patients. It requires lifestyle habits improvement in the absence of effective anti-inflammatory treatment. Besides, reducing ART toxicities remains a crucial therapeutic goal.

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Section: Immune System Activation and Inflammatory Activity Of At In Obese Contextsmentioning

confidence: 99%

Contribution of Adipose Tissue to the Chronic Immune Activation and Inflammation Associated With HIV Infection and Its Treatment

et al. 2021

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“…RAGE belongs to the immunoglobulin superfamily and is expressed in several cell types including alveolar, neuronal, endothelial and immune cells (44)(45)(46)(47). Of note, RAGE expression is increased in most of the pathological conditions associated with COVID-19 severity, such as ageing (48,49), diabetes (50), obesity (51)(52)(53), atherosclerosis (54), cancer (55), chronic obstructive pulmonary disease (56) and ARDS (57).…”

Section: Discussionmentioning

confidence: 99%

RAGE engagement by SARS-CoV-2 enables monocyte infection and underlies COVID-19 severity

Angioni

Bonfanti

Caporale

et al. 2022

Preprint

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The spread of SARS-CoV-2 has fueled the COVID-19 pandemic with its enduring medical and socioeconomic challenges due to subsequent waves and long-term consequences of great concern. Here we charted the molecular basis of COVID-19 pathogenesis, by analysing patients' immune response at single-cell resolution across disease course and severity. This approach uncovered cell subpopulation-specific dysregulation in COVID-19 across disease course and severity and identified a severity-associated activation of the receptor for advanced glycation endproduct (RAGE) pathway in monocytes. In vitro experiments confirmed that monocytes bind the SARS-CoV-2 S1-RBD via RAGE and that RAGE-Spike interactions drive monocyte infection. Our results demonstrate that RAGE is a novel functional receptor of SARS-CoV-2 contributing to COVID-19 severity.

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“…Initially designated as a decoy receptor for the Advanced Glycation End Products generated during hyperglycemic states, RAGE has currently been acknowledged as a signaling receptor for a number of ligands, including S100A7 [31]. RAGE pathway is activated in conditions of de-regulated IGF/Insulin signaling and participates to the establishment of low-grade chronic inflammation and insulin resistance [20,50]. The S100A7/RAGE pathway has been shown to support neoplastic progression in diverse human tumors, including BC.…”

Section: Discussionmentioning

confidence: 99%

“…When released in the extracellular milieu, S100A7 acts as a cytokine-like molecule binding to its receptor RAGE (Receptor for Advanced Glycation End Products), a transmembrane protein belonging to the immunoglobulin superfamily [19]. Previous studies have shown that RAGE signaling is aberrantly activated in conditions of de-regulation of the IGF/Insulin axis, like obesity and T2DM [20]. Furthermore, an activated S100A7/RAGE pathway has been shown to promote angiogenic effects and facilitate breast metastasis dissemination [12].…”

Section: Introductionmentioning

confidence: 99%

Activation of the S100A7/RAGE Pathway by IGF-1 Contributes to Angiogenesis in Breast Cancer

Muoio

Talia

Lappano

et al. 2021

Cancers

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Background: Breast cancer (BC) mortality is increased among obese and diabetic patients. Both obesity and diabetes are associated with dysregulation of both the IGF-1R and the RAGE (Receptor for Advanced Glycation End Products) pathways, which contribute to complications of these disorders. The alarmin S100A7, signaling through the receptor RAGE, prompts angiogenesis, inflammation, and BC progression. Methods: We performed bioinformatic analysis of BC gene expression datasets from published studies. We then used Estrogen Receptor (ER)-positive BC cells, CRISPR-mediated IGF-1R KO BC cells, and isogenic S100A7-transduced BC cells to investigate the role of IGF-1/IGF-1R in the regulation of S100A7 expression and tumor angiogenesis. To this aim, we also used gene silencing and pharmacological inhibitors, and we performed gene expression and promoter studies, western blotting analysis, ChIP and ELISA assays, endothelial cell proliferation and tube formation assay. Results: S100A7 expression correlates with worse prognostic outcomes in human BCs. In BC cells, the IGF-1/IGF-1R signaling engages STAT3 activation and its recruitment to the S100A7 promoter toward S100A7 increase. In human vascular endothelial cells, S100A7 activates RAGE signaling and prompts angiogenic effects. Conclusions: In ER-positive BCs the IGF-1 dependent activation of the S100A7/RAGE signaling in adjacent endothelial cells may serve as a previously unidentified angiocrine effector. Targeting S100A7 may pave the way for a better control of BC, particularly in conditions of unopposed activation of the IGF-1/IGF-1R axis.

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RAGE signalling in obesity and diabetes: focus on the adipose tissue macrophage

Cited by 22 publications

References 25 publications

Contribution of Adipose Tissue to the Chronic Immune Activation and Inflammation Associated With HIV Infection and Its Treatment

Contribution of Adipose Tissue to the Chronic Immune Activation and Inflammation Associated With HIV Infection and Its Treatment

RAGE engagement by SARS-CoV-2 enables monocyte infection and underlies COVID-19 severity

Activation of the S100A7/RAGE Pathway by IGF-1 Contributes to Angiogenesis in Breast Cancer

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