PMC:3897850 / 4614-6949
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3897850","sourcedb":"PMC","sourceid":"3897850","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3897850","text":"RAGE Signaling Pathways\nRAGE and its ligands are highly expressed in developmental stages and enhance survival of neurons during development [15]. After embryonic development, these genes are down-regulated and kept a low expression levels during normal life, except for certain conditions, such as injury and aging [15]. Interestingly, unlike other receptors, expression of RAGE is positively regulated by its ligand stimulation, which means that increasing concentration of ligands leads to up-regulation of RAGE. So, RAGE signals are accelerated more and more by the accumulation of signal stimulants [16].\nRAGE is found on the cell surface of various immune cells, and most of its ligands are mainly secreted by immune cells, including macrophages and dendritic cells; therefore one of the major roles of RAGE is involved in inflammation [7, 14]. Stimulation of RAGE by its ligands activates the proinflammatory transcription factor nuclear factor kappa B (NF-κB), and it then translocates into the nucleus and activates its target genes, including several kinds of cytokines responsible for innate or adaptive immunity [17, 18]. Also, NF-κB can bind to glyoxalase (Glo1) and suppress its inhibitory activity on AGE production [19]. Target genes of NF-κB include anti-apoptotic genes, such as Bcl proteins; therefore, cell survival is also under the control of NF-κB [16]. In addition, the mitogen-activated protein kinase signaling pathway itself can be activated by RAGE stimulation. Specifically, activated RAGE is able to stimulate ERK, p38, and JNK, and it leads to induction of cell proliferation [20]. Another process involved in RAGE signaling is cell migration via transforming growth factor beta (TGF-β) signal cascades. TGF-β is activated by RAGE ligand stimulation and enhances its downstream signals. They include the Ras homolog family and Rho-associated kinase, and activation of these genes leads to stable actin filament formation and cell migration [21]. Due to RAGE signals being concerned with multiple cellular signaling pathways, in particular with immune responses and cell survival, the development of numerous human diseases is associated with it. They include diabetes, inflammatory diseases, cancers, and cardiovascular diseases, and blockade of RAGE is increasingly proposed as a therapeutic target [4].","divisions":[{"label":"Title","span":{"begin":0,"end":23}}],"tracks":[{"project":"2_test","denotations":[{"id":"24465234-11007787-44839203","span":{"begin":142,"end":144},"obj":"11007787"},{"id":"24465234-11007787-44839204","span":{"begin":317,"end":319},"obj":"11007787"},{"id":"24465234-16133426-44839205","span":{"begin":605,"end":607},"obj":"16133426"},{"id":"24465234-24102034-44839206","span":{"begin":843,"end":844},"obj":"24102034"},{"id":"24465234-19589888-44839207","span":{"begin":846,"end":848},"obj":"19589888"},{"id":"24465234-11108954-44839208","span":{"begin":1125,"end":1127},"obj":"11108954"},{"id":"24465234-9091804-44839209","span":{"begin":1129,"end":1131},"obj":"9091804"},{"id":"24465234-19833897-44839210","span":{"begin":1232,"end":1234},"obj":"19833897"},{"id":"24465234-16133426-44839211","span":{"begin":1372,"end":1374},"obj":"16133426"},{"id":"24465234-19292913-44839212","span":{"begin":1608,"end":1610},"obj":"19292913"},{"id":"24465234-9032104-44839213","span":{"begin":1972,"end":1974},"obj":"9032104"},{"id":"24465234-23838007-44839214","span":{"begin":2332,"end":2333},"obj":"23838007"}],"attributes":[{"subj":"24465234-11007787-44839203","pred":"source","obj":"2_test"},{"subj":"24465234-11007787-44839204","pred":"source","obj":"2_test"},{"subj":"24465234-16133426-44839205","pred":"source","obj":"2_test"},{"subj":"24465234-24102034-44839206","pred":"source","obj":"2_test"},{"subj":"24465234-19589888-44839207","pred":"source","obj":"2_test"},{"subj":"24465234-11108954-44839208","pred":"source","obj":"2_test"},{"subj":"24465234-9091804-44839209","pred":"source","obj":"2_test"},{"subj":"24465234-19833897-44839210","pred":"source","obj":"2_test"},{"subj":"24465234-16133426-44839211","pred":"source","obj":"2_test"},{"subj":"24465234-19292913-44839212","pred":"source","obj":"2_test"},{"subj":"24465234-9032104-44839213","pred":"source","obj":"2_test"},{"subj":"24465234-23838007-44839214","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#9493ec","default":true}]}]}}