Lesiones gástricas en pacientes infectados con Helicobacter pylori: expresión de RAGE (receptor de productos de glicosilización avanzada) y otros inmunomarcadores

M, Erik Morales; Rojas, Armando; A, Valeria Monasterio; B, Ileana González; C, Ingrid Figueroa; M, Belarmino Manques; E, Jacqueline Romero; L, Jorge Llanos; M, Eliana Valdés; L, Cecilia Cofré

doi:10.4067/s0034-98872013001000002

Cited by 11 publications

(6 citation statements)

References 44 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, nuclear accumulation and co-localization of RAGE with γH2AX was also observed in several other cell types in response to the DNA-DSBs induced by total body irradiation in an ATM-kinase dependent manner ( Supplementary Figure S11 ). In addition nuclear accumulation of RAGE has been shown previously in other pathological settings, which cause DNA-DSBs, such as H. pylori infection ( 66 ), diabetes ( 67 ) and under severe oxidative stress which affects the nuclear integrity ( 23 – 25 ). Thus, nuclear translocation of RAGE occurs in several pathological settings, which challenge the genomic integrity.…”

Section: Resultsmentioning

confidence: 73%

Homeostatic nuclear RAGE–ATM interaction is essential for efficient DNA repair

Kumar

Fleming

Terjung

et al. 2017

Nucleic Acids Research

View full text Add to dashboard Cite

The integrity of genome is a prerequisite for healthy life. Indeed, defects in DNA repair have been associated with several human diseases, including tissue-fibrosis, neurodegeneration and cancer. Despite decades of extensive research, the spatio-mechanical processes of double-strand break (DSB)-repair, especially the auxiliary factor(s) that can stimulate accurate and timely repair, have remained elusive. Here, we report an ATM-kinase dependent, unforeseen function of the nuclear isoform of the Receptor for Advanced Glycation End-products (nRAGE) in DSB-repair. RAGE is phosphorylated at Serine376 and Serine389 by the ATM kinase and is recruited to the site of DNA-DSBs via an early DNA damage response. nRAGE preferentially co-localized with the MRE11 nuclease subunit of the MRN complex and orchestrates its nucleolytic activity to the ATR kinase signaling. This promotes efficient RPA2S4-S8 and CHK1S345 phosphorylation and thereby prevents cellular senescence, IPF and carcinoma formation. Accordingly, loss of RAGE causatively linked to perpetual DSBs signaling, cellular senescence and fibrosis. Importantly, in a mouse model of idiopathic pulmonary fibrosis (RAGE−/−), reconstitution of RAGE efficiently restored DSB-repair and reversed pathological anomalies. Collectively, this study identifies nRAGE as a master regulator of DSB-repair, the absence of which orchestrates persistent DSB signaling to senescence, tissue-fibrosis and oncogenesis.

show abstract

Section: Resultsmentioning

confidence: 73%

Homeostatic nuclear RAGE–ATM interaction is essential for efficient DNA repair

Kumar

Fleming

Terjung

et al. 2017

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…Helicobacter pylori stimulates expression of RAGE in gastric biopsy specimens, which is thought to be related to cancer-mediated inflammation. 25 RAGE expression affects the antiviral immunity during paucigranulocytic asthma in early-life infection with respiratory syncytial virus in mice. 26 RAGE deficiency impairs clearance of Staphylococcus aureus in sepsis in mice.…”

Section: Discussionmentioning

confidence: 99%

Baicalin modulates apoptosis via RAGE, MAPK, and AP-1 in vascular endothelial cells duringHaemophilus parasuisinvasion

Zhao

Xiong

et al. 2019

Innate Immun

View full text Add to dashboard Cite

Glässer’s disease, caused by Haemophilus parasuis, is a chronic disease related to an inflammatory immune response. Baicalin exerts important biological functions. In this study, we explored the protective efficacy of treatment with baicalin and the potential mechanism of activation of the MAPK signaling pathway in porcine aortic vascular endothelial cells (PAVECs) induced by H. parasuis. H. parasuis stimulated expression of receptor for advanced glycation end products, induced a significant increase in the level of protein kinase-α and protein kinase-δ phosphorylation, and significantly up-regulated ERK, c-Jun N-terminal kinase, and p38 phosphorylation in PAVECs. H. parasuis also up-regulated the levels of apoptotic genes ( Bax, C-myc, and Fasl) and the expression levels of c-Jun and c-Fos, and induced S-phase arrest in PAVECs. However, treatment with baicalin inhibited expression of RAGE, suppressed H. parasuis-induced protein kinase-α and protein kinase-δ phosphorylation, reduced ERK, c-Jun N-terminal kinase, and p38 phosphorylation, down-regulated apoptotic genes ( Bax, C-myc, and Fasl), attenuated phospho-c-Jun production from the extracellular to the nuclei, and reversed S-phase arrest in PAVECs. In conclusion, baicalin treatment inhibited the MAPK signaling pathway, thereby achieving its anti-inflammatory responses, which provides a new strategy to control H. parasuis infection.

show abstract

“…Similarly, in a previous study, the HMGB1 expression in gastric cancer tissues was increased as compared to that in non-cancerous tissues ( 54 ). Moreover, a markedly higher percentage of RAGE expression was found in H. pylori -infected biopsies with dysplasia or in situ carcinoma as compared to that in the control groups ( 55 ). Most importantly, it has been proven that overexpressed HMGB1 enhances IL-8 secretion in tumor cells and over-secreted IL-8 promotes EMT activation in gastric cancer cells ( 56 ).…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells

et al. 2016

View full text Add to dashboard Cite

Helicobacter pylori infection is associated with several gastrointestinal disorders in the human population worldwide. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. The interaction between HMGB1 and receptor for advanced glycation end-products (RAGE) triggers nuclear factor (NF)-κB expression, which in turn stimulates the release of proinflammatory cytokines, such as interleukin (IL)-8, and enhances the inflammatory response. However, how H. pylori activates HMGB1 expression and mobilizes RAGE into cholesterol-rich microdomains in gastric epithelial cells to promote inflammation has not been explored. In this study, we found that HMGB1 and RAGE expression increased significantly in H. pylori-infected cells compared with -uninfected cells. Blocking HMGB1 by neutralizing antibody abrogated H. pylori-elicited RAGE, suggesting that RAGE expression follows HMGB1 production, and silenced RAGE-attenuated H. pylori-mediated NF-κB activation and IL-8 production. Furthermore, significantly more RAGE was present in detergent-resistant membranes extracted from H. pylori-infected cells than in those from -uninfected cells, indicating that H. pylori exploited cholesterol to induce the HMGB1 signaling pathway. These results indicate that HMGB1 plays a crucial role in H. pylori-induced inflammation in gastric epithelial cells, which may be valuable in developing treatments for H. pylori-associated diseases.

show abstract

Lesiones gástricas en pacientes infectados con Helicobacter pylori: expresión de RAGE (receptor de productos de glicosilización avanzada) y otros inmunomarcadores

Abstract: Background: Inflammation is a common phenomenon present in gastric mucosa of patients infected with H. pylori. Activation of the RAGE/multiligand axis is (Rev Med Chile 2013; 141: 1240-1248.

Cited by 11 publications

References 44 publications

Homeostatic nuclear RAGE–ATM interaction is essential for efficient DNA repair

Homeostatic nuclear RAGE–ATM interaction is essential for efficient DNA repair

Baicalin modulates apoptosis via RAGE, MAPK, and AP-1 in vascular endothelial cells duringHaemophilus parasuisinvasion

Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells

Contact Info

Product

Resources

About