Ligands of RAGE-Proteins: Role in Intercellular Communication and Pathogenesis of Inflammation

Uspenskaya, Yu. A.; Kоmleva, Yu. K.; Пожиленкова, Е. А.; Salmin, Vladimir V.; Lopatina, Olga; Fursov, A. A.; Lavrentiev, Pavel; Belova, Olga A.; Салмина, А. Б.

doi:10.15690/vramn566

Cited by 14 publications

(6 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It significantly increases the expression of IL-1β, IL-6, and TNF-α by stimulating peripheral blood mononuclear cells, inducing TLR4-mediated inflammatory signaling in mononuclear cells and activating transcription factor (NF)-κ B, extracellular signal-regulated kinase 1/2, and P38 [ 21 ]. S100A4 multimers (active form) can also stimulate synovial fibroblasts and regulate apoptosis [ 22 ]. These results suggest that S100A4 activates immune and inflammatory responses.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Role of the S100 protein family in rheumatoid arthritis

Wang

et al. 2022

Arthritis Res Ther

View full text Add to dashboard Cite

Rheumatoid arthritis is a chronic systemic autoimmune disease characterized by synovial hyperplasia, inflammatory cell infiltration, and proliferation of inflammatory tissue (angiogranuloma). The destruction of joints and surrounding tissues eventually causes joint deformities and dysfunction or even loss. The S100 protein family is one of the biggest subtribes in the calcium-binding protein family and has more than 20 members. The overexpression of most S100 proteins in rheumatoid arthritis is closely related to its pathogenesis. This paper reviews the relationship between S100 proteins and the occurrence and development of rheumatoid arthritis. It will provide insights into the development of new clinical diagnostic markers and therapeutic targets for rheumatoid arthritis.

show abstract

Section: Introductionmentioning

confidence: 99%

“…Extracellular S100B is associated with RAGE signaling in chondrocytes, which may be the mechanism underlying osteogenesis in RA [ 22 ]. S100A8/A9 induces proteoglycan decomposition, chondrocyte apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Role of the S100 protein family in rheumatoid arthritis

Wang

et al. 2022

Arthritis Res Ther

View full text Add to dashboard Cite

show abstract

“…Notably, the interactions between microglia and other cell types, including neurons, astrocytes, endothelial cells, and stem cells, as well as the underlying mechanisms, are complex, and these might involve intriguing roles of the receptor of advanced glycation end products (RAGEs), S100B, high-mobility group box 1 (HMGB1), and NADPH oxidase . RAGE, a cell-surface receptor that can bind to various ligands, including advanced glycation end products (AGEs), HMGB1, S100 proteins, and amyloid-β (Aβ), is mainly expressed in cortical and spinal motor neurons, astrocytes, microglia, and endothelial cells and is expressed at a high level in the developing nervous system. − In adult animals, RAGE is expressed at a low level under physiological conditions but is drastically increased under chronic inflammation because of the accumulation of various RAGE ligands. ,, With regard to cerebral ischemia, the results of in vitro and in vivo experiments have indicated that RAGE expression in brain tissues or nerve cells is increased after hypoxic injury in a time-dependent manner ,− and is associated with neuronal apoptosis and the severity of cerebral infarction, , and this increase has been confirmed in stroke patients; moreover, the increased RAGE expression probably accelerates ischemia-induced neuronal death through activation of inflammatory pathways. − These findings indicate that RAGE potentially plays a critical role in cerebral infarction.…”

Section: Introductionmentioning

confidence: 99%

FPS-ZM1 Alleviates Neuroinflammation in Focal Cerebral Ischemia Rats via Blocking Ligand/RAGE/DIAPH1 Pathway

Shen

Zhang

et al. 2020

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Receptor for advanced glycation end products (RAGEs), a multiligand receptor belonging to the cell-surface immunoglobulin superfamily, has been reported to play a crucial role in neuroinflammation and neurodegenerative diseases. Here, we tested our hypothesis that the RAGE-specific antagonist FPS-ZM1 is neuroprotective against ischemic brain injury. Distal middle cerebral artery occlusion (MCAO) or sham operation was performed on anesthetized Sprague−Dawley male rats (n = 60), which were then treated with FPS-ZM1 or vehicle (four groups in total = Vehicle + MCAO, FPS-ZM1 + MCAO, Vehicle + sham, and FPS-ZM1 + sham). After 1 week, neurological function was evaluated, and then, brain tissues were collected for 2,3,5triphenyltetrazolium chloride staining, Nissl staining, TUNEL staining, Western blotting, and immunohistochemical analyses. FPS-ZM1 treatment after MCAO markedly attenuated neurological deficits and reduced the infarct area. More interestingly, FPS-ZM1 inhibited ischemia-induced astrocytic activation and microgliosis and decreased the elevated levels of proinflammatory cytokines. Furthermore, FPS-ZM1 blocked the increase in the level of RAGE and, notably, of DIAPH1, the key cytoplasmic hub for RAGEligand-mediated activation of cellular signaling. Accordingly, FPS-ZM1 also reversed the MCAO-induced increase in phosphorylation of NF-κB targets that are potentially downstream from RAGE/DIAPH1. Our findings reveal that FPS-ZM1 treatment reduces neuroinflammation in rats with focal cerebral ischemia and further suggest that the ligand/RAGE/DIAPH1 pathway contributes to this FPS-ZM1-mediated alleviation of neuroinflammation.

show abstract

“…Besides the pro‐ and anti‐inflammatory cells and mediators, RAGE (Receptor for Advanced Glycation Endproducts), a receptor capable of interacting with signaling molecules, are involved in the inflammatory process (Deane et al, 2004; Kierdorf and Fritz, 2013). RAGE comprises one of the receptors for non‐enzymatic non‐glycated adducts (AGEs), playing a key role in the inflammatory process because of their interactions and the ability to induce secretion of cytokines and chemokines (Schmidt et al, 2001; Uspenskaya et al, 2015). RAGE is considered a key mediator of several physiological, as well as pathological (e.g.…”

Section: Introductionmentioning

confidence: 99%

Administration of branched‐chain amino acids increases the susceptibility to lipopolysaccharide‐induced inflammation in young Wistar rats

Wessler

Ramos

Pasquali

et al. 2019

Intl J of Devlp Neuroscience

View full text Add to dashboard Cite

Maple Syrup Urine Disease (MSUD) is an inborn error of the metabolism caused by defects in the branched a‐ketoacid dehydrogenase complex (BCKDC), leading to the accumulation of branched chain amino acids (BCAAs) (leucine, isoleucine and valine). Patients with MSUD present a series of neurological dysfunction. Recent studies have been associated the brain damage in the MSUD with inflammation and immune system activation. MSUD patients die within a few months of life due to recurrent metabolic crises and neurologic deterioration, often precipitated by infection or other stresses. In this regard, our previous results showed that the inflammatory process, induced by lipopolysaccharide (LPS), associated with high levels of BCAAs causes blood‐brain barrier (BBB) breakdown due to hyperactivation of MMPs. Thus, we hypothesize that the synergistic action between high concentrations of BCAAs (H‐BCAAs) and LPS on BBB permeability and hyperactivation of MMPs could be through an increase in the production of cytokines and RAGE protein levels. We observed that high levels of BCAA in infant rats are related to increased brain inflammation induced by LPS administration. In addition, BCAA exposure led to an increase on brain RAGE expression of young rats. The brain inflammation was characterized by enhanced levels of interleukin 1 β (IL‐1β), interleukin 6 (IL‐6), tumor necrosis factor‐α (TNF‐α) and Interferon‐ γ (IFN‐γ), and decreased content of interleukin‐10 (IL‐10). Therefore, MSUD is associated with a more intense neuroinflammation induced by LPS infection.

show abstract

Ligands of RAGE-Proteins: Role in Intercellular Communication and Pathogenesis of Inflammation

Abstract: The review contains data on the diversity of endogenous ligands of RAGE receptors (receptor for advanced glycation end products) that play an important role in the signal transduction in (patho) physiological conditions. RAGE takes part in various physiological

Cited by 14 publications

References 74 publications

Role of the S100 protein family in rheumatoid arthritis

Role of the S100 protein family in rheumatoid arthritis

FPS-ZM1 Alleviates Neuroinflammation in Focal Cerebral Ischemia Rats via Blocking Ligand/RAGE/DIAPH1 Pathway

Administration of branched‐chain amino acids increases the susceptibility to lipopolysaccharide‐induced inflammation in young Wistar rats

Contact Info

Product

Resources

About