Therapeutic effects of antigen affinity-purified polyclonal anti-receptor of advanced glycation end-product (RAGE) antibodies on cholestasis-induced liver injury in rats

Xia, Peng; Deng, Qing; Gao, Jin; Yu, Xiaolan; Zhang, Yang; Li, Jingjing; Guan, Wen; Hu, Jianjun; Tan, Quanhui; Zhou, Liang; Wang, Han; Yuan, Yunsheng; Yu, Yang

doi:10.1016/j.ejphar.2016.03.017

Cited by 10 publications

(3 citation statements)

References 39 publications

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“…Also, the activation of HSC and NF-κB was reduced in siRNA-treated animals, attenuating the initiation and progress of fibrosis [ 167 ]. Additional studies revealed protective effects of anti-RAGE antibodies in BDL-induced acute liver injury [ 168 , 169 ].…”

Section: Glo-i Ages and Rage In Chronic Liver Injurymentioning

confidence: 99%

The Role of Glyoxalase-I (Glo-I), Advanced Glycation Endproducts (AGEs), and Their Receptor (RAGE) in Chronic Liver Disease and Hepatocellular Carcinoma (HCC)

Hollenbach¹

2017

IJMS

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Glyoxalase-I (Glo-I) and glyoxalase-II (Glo-II) comprise the glyoxalase system and are responsible for the detoxification of methylglyoxal (MGO). MGO is formed non-enzymatically as a by-product, mainly in glycolysis, and leads to the formation of advanced glycation endproducts (AGEs). AGEs bind to their receptor, RAGE, and activate intracellular transcription factors, resulting in the production of pro-inflammatory cytokines, oxidative stress, and inflammation. This review will focus on the implication of the Glo-I/AGE/RAGE system in liver injury and hepatocellular carcinoma (HCC). AGEs and RAGE are upregulated in liver fibrosis, and the silencing of RAGE reduced collagen deposition and the tumor growth of HCC. Nevertheless, data relating to Glo-I in fibrosis and cirrhosis are preliminary. Glo-I expression was found to be reduced in early and advanced cirrhosis with a subsequent increase of MGO-levels. On the other hand, pharmacological modulation of Glo-I resulted in the reduced activation of hepatic stellate cells and therefore reduced fibrosis in the CCl4-model of cirrhosis. Thus, current research highlighted the Glo-I/AGE/RAGE system as an interesting therapeutic target in chronic liver diseases. These findings need further elucidation in preclinical and clinical studies.

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Section: Glo-i Ages and Rage In Chronic Liver Injurymentioning

confidence: 99%

The Role of Glyoxalase-I (Glo-I), Advanced Glycation Endproducts (AGEs), and Their Receptor (RAGE) in Chronic Liver Disease and Hepatocellular Carcinoma (HCC)

Hollenbach¹

2017

IJMS

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“…Expression of RAGE was has been reported as higher in cholangiocytes when compared to other cell types in cholestatic livers (48) and in proliferating bile ducts after bile duct ligation, (49) where the administration of anti-RAGE antibodies attenuated bile duct proliferation and liver fibrosis. (50) This is particularly relevant to our findings of a connectome gene enrichment in the AGE-RAGE pathway. Directly testing this pathway in cholangiocytes, we showed that HMGB1, a damage-associated molecular pattern released from injured cells, (5) induces cholangiocyte proliferation and expression of IL6 and TGFB1 mRNAs through RAGE.…”

Section: Discussionmentioning

confidence: 57%

“…Expression of RAGE was has been reported as higher in cholangiocytes when compared to other cell types in cholestatic livers and in proliferating bile ducts after bile duct ligation, where the administration of anti‐RAGE antibodies attenuated bile duct proliferation and liver fibrosis . This is particularly relevant to our findings of a connectome gene enrichment in the AGE‐RAGE pathway.…”

Section: Discussionmentioning

confidence: 99%

Gene‐disease associations identify a connectome with shared molecular pathways in human cholangiopathies

Luo¹,

Jegga

Bezerra³

2018

Hepatology

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Anti-RAGE antibody selectively blocks acute systemic inflammatory responses to LPS in serum, liver, CSF and striatum

Gasparotto

Ribeiro

Bortolin

et al. 2017

Brain, Behavior, and Immunity

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Systemic inflammation induces transient or permanent dysfunction in the brain by exposing it to soluble inflammatory mediators. The receptor for advanced glycation endproducts (RAGE) binds to distinct ligands mediating and increasing inflammatory processes. In this study we used an LPS-induced systemic inflammation model in rats to investigate the effect of blocking RAGE in serum, liver, cerebrospinal fluid (CSF) and brain (striatum, prefrontal cortex, ventral tegmental area and substantia nigra). Intraperitoneal injection of RAGE antibody (50μg/kg) was followed after 1h by a single LPS (5mg/kg) intraperitoneal injection. Twenty-four hours later, tissues were isolated for analysis. RAGE antibody reduced LPS-induced inflammatory effects in both serum and liver; the levels of proinflammatory cytokines (TNF-α, IL-1β) were decreased and the phosphorylation/activation of RAGE downstream targets (ERK1/2, IκB and p65) in liver were significantly attenuated. RAGE antibody prevented LPS-induced effects on TNF-α and IL-1β in CSF. In striatum, RAGE antibody inhibited increases in IL-1β, Iba-1, GFAP, phospho-ERK1/2 and phospho-tau (ser202), as well as the decrease in synaptophysin levels. These effects were caused by systemic RAGE inhibition, as RAGE antibody did not cross the blood-brain barrier. RAGE antibody also prevented striatal lipoperoxidation and activation of mitochondrial complex II. In conclusion, blockade of RAGE is able to inhibit inflammatory responses induced by LPS in serum, liver, CSF and brain.

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Therapeutic effects of antigen affinity-purified polyclonal anti-receptor of advanced glycation end-product (RAGE) antibodies on cholestasis-induced liver injury in rats

Cited by 10 publications

References 39 publications

The Role of Glyoxalase-I (Glo-I), Advanced Glycation Endproducts (AGEs), and Their Receptor (RAGE) in Chronic Liver Disease and Hepatocellular Carcinoma (HCC)

The Role of Glyoxalase-I (Glo-I), Advanced Glycation Endproducts (AGEs), and Their Receptor (RAGE) in Chronic Liver Disease and Hepatocellular Carcinoma (HCC)

Gene‐disease associations identify a connectome with shared molecular pathways in human cholangiopathies

Anti-RAGE antibody selectively blocks acute systemic inflammatory responses to LPS in serum, liver, CSF and striatum

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